Nanoparticle Strategies to Improve the Delivery of Anticancer Drugs across the Blood–Brain Barrier to Treat Brain Tumors
Abstract
:1. Introduction
1.1. Primary Brain and Other Central Nervous System Tumors
1.2. Blood–Brain Barrier
1.3. Nanoparticle Strategies in Neuro-Oncology
2. Nanoparticle Classes under Investigation as Drug Delivery Systems for Brain Tumors
2.1. Lipid-Based Nanoparticles
2.2. Polymeric Nanoparticles
2.3. Inorganic Nanoparticles
2.4. Biological Nanoparticles
3. Engineered Nanoparticles to Enhance Targeted Drug Delivery to CNS Tumors
3.1. Nanoparticle Clearance and Blood Circulation Time
3.2. Nanoparticle Strategies to Enhance Drug Delivery Past the BBB
3.2.1. Nanoparticle Modifications to Increase BBB Passage
3.2.2. Cell-Mediated and Cell-Mimicking Drug Delivery over the BBB
3.2.3. Bypassing the BBB
3.3. Nanoparticle Modifications to Increase Delivery to Brain Tumor Cells
4. Novel Strategies and Future Directions
5. Summary and Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Ostrom, Q.T.; Cioffi, G.; Waite, K.; Kruchko, C.; Barnholtz-Sloan, J.S. CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2014–2018. Neuro Oncol. 2021, 23, iii1–iii105. [Google Scholar] [CrossRef] [PubMed]
- Girardi, F.; Matz, M.; Stiller, C.; You, H.; Marcos Gragera, R.; Valkov, M.Y.; Bulliard, J.-L.; De, P.; Morrison, D.; Wanner, M. Global survival trends for brain tumors, by histology: Analysis of individual records for 556,237 adults diagnosed in 59 countries during 2000–2014 (CONCORD-3). Neuro Oncol. 2023, 25, 580–592. [Google Scholar] [CrossRef] [PubMed]
- Gittleman, H.; Boscia, A.; Ostrom, Q.T.; Truitt, G.; Fritz, Y.; Kruchko, C.; Barnholtz-Sloan, J.S. Survivorship in adults with malignant brain and other central nervous system tumor from 2000–2014. Neuro Oncol. 2018, 20, vii6–vii16. [Google Scholar] [CrossRef] [PubMed]
- Ostrom, Q.T.; Price, M.; Ryan, K.; Edelson, J.; Neff, C.; Cioffi, G.; Waite, K.A.; Kruchko, C.; Barnholtz-Sloan, J.S. CBTRUS Statistical Report: Pediatric Brain Tumor Foundation Childhood and Adolescent Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2014–2018. Neuro Oncol. 2022, 24, iii1–iii38. [Google Scholar] [CrossRef]
- Girardi, F.; Di Carlo, V.; Stiller, C.; Gatta, G.; Woods, R.R.; Visser, O.; Lacour, B.; Tucker, T.C.; Coleman, M.P.; Allemani, C. Global survival trends for brain tumors, by histology: Analysis of individual records for 67,776 children diagnosed in 61 countries during 2000–2014 (CONCORD-3). Neuro Oncol. 2023, 25, 593–606. [Google Scholar] [CrossRef]
- Warren, K.E. Diffuse intrinsic pontine glioma: Poised for progress. Front. Oncol. 2012, 2, 205. [Google Scholar] [CrossRef] [Green Version]
- Pollack, I.F.; Agnihotri, S.; Broniscer, A. Childhood brain tumors: Current management, biological insights, and future directions. J. Neurosurg. Pediatr. 2019, 23, 261–273. [Google Scholar] [CrossRef] [Green Version]
- Schaff, L.R.; Mellinghoff, I.K. Glioblastoma and Other Primary Brain Malignancies in Adults: A Review. JAMA 2023, 329, 574–587. [Google Scholar] [CrossRef]
- Louis, D.N.; Perry, A.; Wesseling, P.; Brat, D.J.; Cree, I.A.; Figarella-Branger, D.; Hawkins, C.; Ng, H.K.; Pfister, S.M.; Reifenberger, G.; et al. The 2021 WHO Classification of Tumors of the Central Nervous System: A summary. Neuro Oncol. 2021, 23, 1231–1251. [Google Scholar] [CrossRef]
- Wen, P.Y.; Weller, M.; Lee, E.Q.; Alexander, B.M.; Barnholtz-Sloan, J.S.; Barthel, F.P.; Batchelor, T.T.; Bindra, R.S.; Chang, S.M.; Chiocca, E.A.; et al. Glioblastoma in adults: A Society for Neuro Oncol. (SNO) and European Society of Neuro-Oncology (EANO) consensus review on current management and future directions. Neuro Oncol. 2020, 22, 1073–1113. [Google Scholar] [CrossRef]
- Stupp, R.; Mason, W.P.; van den Bent, M.J.; Weller, M.; Fisher, B.; Taphoorn, M.J.; Belanger, K.; Brandes, A.A.; Marosi, C.; Bogdahn, U.; et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N. Engl. J. Med. 2005, 352, 987–996. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Fang, F.Y.; Rosenblum, J.S.; Ho, W.S.; Heiss, J.D. New Developments in the Pathogenesis, Therapeutic Targeting, and Treatment of Pediatric Medulloblastoma. Cancers 2022, 14, 2285. [Google Scholar] [CrossRef] [PubMed]
- Mendes, M.; Sousa, J.J.; Pais, A.; Vitorino, C. Targeted Theranostic Nanoparticles for Brain Tumor Treatment. Pharmaceutics 2018, 10, 181. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bellavance, M.A.; Blanchette, M.; Fortin, D. Recent advances in blood-brain barrier disruption as a CNS delivery strategy. AAPS J. 2008, 10, 166–177. [Google Scholar] [CrossRef] [Green Version]
- Haumann, R.; Videira, J.C.; Kaspers, G.J.L.; van Vuurden, D.G.; Hulleman, E. Overview of Current Drug Delivery Methods Across the Blood-Brain Barrier for the Treatment of Primary Brain Tumors. CNS Drugs 2020, 34, 1121–1131. [Google Scholar] [CrossRef]
- Oberoi, R.K.; Parrish, K.E.; Sio, T.T.; Mittapalli, R.K.; Elmquist, W.F.; Sarkaria, J.N. Strategies to improve delivery of anticancer drugs across the blood-brain barrier to treat glioblastoma. Neuro Oncol. 2016, 18, 27–36. [Google Scholar] [CrossRef] [Green Version]
- Daneman, R.; Prat, A. The blood-brain barrier. Cold Spring Harb. Perspect. Biol. 2015, 7, a020412. [Google Scholar] [CrossRef] [Green Version]
- Obermeier, B.; Daneman, R.; Ransohoff, R.M. Development, maintenance and disruption of the blood-brain barrier. Nat. Med. 2013, 19, 1584–1596. [Google Scholar] [CrossRef] [Green Version]
- Pardridge, W.M. The blood-brain barrier: Bottleneck in brain drug development. NeuroRX 2005, 2, 3–14. [Google Scholar] [CrossRef]
- Abbott, N.J.; Patabendige, A.A.; Dolman, D.E.; Yusof, S.R.; Begley, D.J. Structure and function of the blood-brain barrier. Neurobiol. Dis. 2010, 37, 13–25. [Google Scholar] [CrossRef]
- Pardridge, W.M. The Isolated Brain Microvessel: A Versatile Experimental Model of the Blood-Brain Barrier. Front. Physiol. 2020, 11, 398. [Google Scholar] [CrossRef] [PubMed]
- Abbott, N.J.; Rönnbäck, L.; Hansson, E. Astrocyte-endothelial interactions at the blood-brain barrier. Nat. Rev. Neurosci. 2006, 7, 41–53. [Google Scholar] [CrossRef] [PubMed]
- Liu, L.R.; Liu, J.C.; Bao, J.S.; Bai, Q.Q.; Wang, G.Q. Interaction of Microglia and Astrocytes in the Neurovascular Unit. Front. Immunol. 2020, 11, 1024. [Google Scholar] [CrossRef] [PubMed]
- Xu, L.; Nirwane, A.; Yao, Y. Basement membrane and blood-brain barrier. Stroke Vasc. Neurol. 2019, 4, 78–82. [Google Scholar] [CrossRef] [Green Version]
- Uemura, M.T.; Maki, T.; Ihara, M.; Lee, V.M.Y.; Trojanowski, J.Q. Brain Microvascular Pericytes in Vascular Cognitive Impairment and Dementia. Front. Aging Neurosci. 2020, 12, 80. [Google Scholar] [CrossRef] [Green Version]
- Ballabh, P.; Braun, A.; Nedergaard, M. The blood-brain barrier: An overview: Structure, regulation, and clinical implications. Neurobiol. Dis. 2004, 16, 1–13. [Google Scholar] [CrossRef] [PubMed]
- Jia, W.; Lu, R.; Martin, T.A.; Jiang, W.G. The role of claudin-5 in blood-brain barrier (BBB) and brain metastases (review). Mol. Med. Rep. 2014, 9, 779–785. [Google Scholar] [CrossRef] [Green Version]
- Lochhead, J.J.; Yang, J.; Ronaldson, P.T.; Davis, T.P. Structure, Function, and Regulation of the Blood-Brain Barrier Tight Junction in Central Nervous System Disorders. Front. Physiol. 2020, 11, 914. [Google Scholar] [CrossRef]
- Tamai, I.; Tsuji, A. Transporter-mediated permeation of drugs across the blood-brain barrier. J. Pharm. Sci. 2000, 89, 1371–1388. [Google Scholar] [CrossRef]
- Harilal, S.; Jose, J.; Parambi, D.G.T.; Kumar, R.; Unnikrishnan, M.K.; Uddin, M.S.; Mathew, G.E.; Pratap, R.; Marathakam, A.; Mathew, B. Revisiting the blood-brain barrier: A hard nut to crack in the transportation of drug molecules. Brain Res. Bull. 2020, 160, 121–140. [Google Scholar] [CrossRef]
- Sun, H.; Dai, H.; Shaik, N.; Elmquist, W.F. Drug efflux transporters in the CNS. Adv. Drug Deliv. Rev. 2003, 55, 83–105. [Google Scholar] [CrossRef] [PubMed]
- Löscher, W.; Potschka, H. Blood-brain barrier active efflux transporters: ATP-binding cassette gene family. NeuroRx 2005, 2, 86–98. [Google Scholar] [CrossRef] [PubMed]
- Singleton, W.G.B.; Bienemann, A.S.; Woolley, M.; Johnson, D.; Lewis, O.; Wyatt, M.J.; Damment, S.J.P.; Boulter, L.J.; Killick-Cole, C.L.; Asby, D.J.; et al. The distribution, clearance, and brainstem toxicity of panobinostat administered by convection-enhanced delivery. J. Neurosurg. Pediatr. PED 2018, 22, 288–296. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chaves, C.; Declèves, X.; Taghi, M.; Menet, M.-C.; Lacombe, J.; Varlet, P.; Olaciregui, N.G.; Carcaboso, A.M.; Cisternino, S. Characterization of the Blood–Brain Barrier Integrity and the Brain Transport of SN-38 in an Orthotopic Xenograft Rat Model of Diffuse Intrinsic Pontine Glioma. Pharmaceutics 2020, 12, 399. [Google Scholar] [CrossRef] [PubMed]
- Miklja, Z.; Yadav, V.N.; Cartaxo, R.T.; Siada, R.; Thomas, C.C.; Cummings, J.R.; Mullan, B.; Stallard, S.; Paul, A.; Bruzek, A.K.; et al. Everolimus improves the efficacy of dasatinib in PDGFRα-driven glioma. J. Clin. Investig. 2020, 130, 5313–5325. [Google Scholar] [CrossRef] [PubMed]
- Oh, J.H.; Power, E.A.; Zhang, W.; Daniels, D.J.; Elmquist, W.F. Murine Central Nervous System and Bone Marrow Distribution of the Aurora A Kinase Inhibitor Alisertib: Pharmacokinetics and Exposure at the Sites of Efficacy and Toxicity. J. Pharmacol. Exp. Ther. 2022, 383, 44–55. [Google Scholar] [CrossRef]
- Laramy, J.K.; Kim, M.; Parrish, K.E.; Sarkaria, J.N.; Elmquist, W.F. Pharmacokinetic Assessment of Cooperative Efflux of the Multitargeted Kinase Inhibitor Ponatinib Across the Blood-Brain Barrier. J. Pharmacol. Exp. Ther. 2018, 365, 249–261. [Google Scholar] [CrossRef] [Green Version]
- Warren, K.E. Beyond the Blood:Brain Barrier: The Importance of Central Nervous System (CNS) Pharmacokinetics for the Treatment of CNS Tumors, Including Diffuse Intrinsic Pontine Glioma. Front. Oncol. 2018, 8, 239. [Google Scholar] [CrossRef] [Green Version]
- Bhowmik, A.; Khan, R.; Ghosh, M.K. Blood brain barrier: A challenge for effectual therapy of brain tumors. Biomed. Res. Int. 2015, 2015, 320941. [Google Scholar] [CrossRef] [Green Version]
- Banks, W.A. From blood–brain barrier to blood–brain interface: New opportunities for CNS drug delivery. Nat. Rev. Drug Discov. 2016, 15, 275–292. [Google Scholar] [CrossRef]
- Rathi, S.; Griffith, J.I.; Zhang, W.; Zhang, W.; Oh, J.H.; Talele, S.; Sarkaria, J.N.; Elmquist, W.F. The influence of the blood-brain barrier in the treatment of brain tumours. J. Intern. Med. 2022, 292, 3–30. [Google Scholar] [CrossRef] [PubMed]
- Varlet, P.; Le Teuff, G.; Le Deley, M.C.; Giangaspero, F.; Haberler, C.; Jacques, T.S.; Figarella-Branger, D.; Pietsch, T.; Andreiuolo, F.; Deroulers, C.; et al. WHO grade has no prognostic value in the pediatric high-grade glioma included in the HERBY trial. Neuro Oncol. 2020, 22, 116–127. [Google Scholar] [CrossRef] [PubMed]
- Sarkaria, J.N.; Hu, L.S.; Parney, I.F.; Pafundi, D.H.; Brinkmann, D.H.; Laack, N.N.; Giannini, C.; Burns, T.C.; Kizilbash, S.H.; Laramy, J.K.; et al. Is the blood-brain barrier really disrupted in all glioblastomas? A critical assessment of existing clinical data. Neuro Oncol. 2018, 20, 184–191. [Google Scholar] [CrossRef] [PubMed]
- Pafundi, D.H.; Laack, N.N.; Youland, R.S.; Parney, I.F.; Lowe, V.J.; Giannini, C.; Kemp, B.J.; Grams, M.P.; Morris, J.M.; Hoover, J.M.; et al. Biopsy validation of 18F-DOPA PET and biodistribution in gliomas for neurosurgical planning and radiotherapy target delineation: Results of a prospective pilot study. Neuro Oncol. 2013, 15, 1058–1067. [Google Scholar] [CrossRef]
- Himes, B.T.; Zhang, L.; Daniels, D.J. Treatment Strategies in Diffuse Midline Gliomas With the H3K27M Mutation: The Role of Convection-Enhanced Delivery in Overcoming Anatomic Challenges. Front. Oncol. 2019, 9, 31. [Google Scholar] [CrossRef] [Green Version]
- Ek, C.J.; Wong, A.; Liddelow, S.A.; Johansson, P.A.; Dziegielewska, K.M.; Saunders, N.R. Efflux mechanisms at the developing brain barriers: ABC-transporters in the fetal and postnatal rat. Toxicol. Lett. 2010, 197, 51–59. [Google Scholar] [CrossRef]
- Saunders, N.R.; Liddelow, S.A.; Dziegielewska, K.M. Barrier mechanisms in the developing brain. Front. Pharmacol. 2012, 3, 46. [Google Scholar] [CrossRef] [Green Version]
- Verscheijden, L.F.M.; van Hattem, A.C.; Pertijs, J.; de Jongh, C.A.; Verdijk, R.M.; Smeets, B.; Koenderink, J.B.; Russel, F.G.M.; de Wildt, S.N. Developmental patterns in human blood-brain barrier and blood-cerebrospinal fluid barrier ABC drug transporter expression. Histochem. Cell Biol. 2020, 154, 265–273. [Google Scholar] [CrossRef]
- Mazumder, S.; Dewangan, A.K.; Pavurala, N. Enhanced dissolution of poorly soluble antiviral drugs from nanoparticles of cellulose acetate based solid dispersion matrices. Asian J. Pharm. Sci. 2017, 12, 532–541. [Google Scholar] [CrossRef]
- Caraway, C.A.; Gaitsch, H.; Wicks, E.E.; Kalluri, A.; Kunadi, N.; Tyler, B.M. Polymeric Nanoparticles in Brain Cancer Therapy: A Review of Current Approaches. Polymers 2022, 14, 2963. [Google Scholar] [CrossRef]
- Anselmo, A.C.; Mitragotri, S. Nanoparticles in the clinic: An update. Bioeng. Transl. Med. 2019, 4, e10143. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Genovesi, L.A.; Puttick, S.; Millar, A.; Kojic, M.; Ji, P.; Lagendijk, A.K.; Brighi, C.; Bonder, C.S.; Adolphe, C.; Wainwright, B.J. Patient-derived orthotopic xenograft models of medulloblastoma lack a functional blood-brain barrier. Neuro Oncol. 2021, 23, 732–742. [Google Scholar] [CrossRef] [PubMed]
- Becker, A.; Sells, B.; Haque, S.; Chakravarti, A. Tumor Heterogeneity in Glioblastomas: From Light Microscopy to Molecular Pathology. Cancers 2021, 13, 761. [Google Scholar] [CrossRef]
- Ruan, S.; Zhou, Y.; Jiang, X.; Gao, H. Rethinking CRITID Procedure of Brain Targeting Drug Delivery: Circulation, Blood Brain Barrier Recognition, Intracellular Transport, Diseased Cell Targeting, Internalization, and Drug Release. Adv. Sci. 2021, 8, 2004025. [Google Scholar] [CrossRef]
- Niu, X.; Chen, J.; Gao, J. Nanocarriers as a powerful vehicle to overcome blood-brain barrier in treating neurodegenerative diseases: Focus on recent advances. Asian J. Pharm. Sci. 2019, 14, 480–496. [Google Scholar] [CrossRef] [PubMed]
- Dong, X. Current Strategies for Brain Drug Delivery. Theranostics 2018, 8, 1481–1493. [Google Scholar] [CrossRef] [PubMed]
- Rueda, F.; Cruz, L.J. Targeting the Brain with Nanomedicine. Curr. Pharm. Des. 2017, 23, 1879–1896. [Google Scholar] [CrossRef]
- Koog, L.; Gandek, T.B.; Nagelkerke, A. Liposomes and Extracellular Vesicles as Drug Delivery Systems: A Comparison of Composition, Pharmacokinetics, and Functionalization. Adv. Healthc. Mater. 2022, 11, 2100639. [Google Scholar] [CrossRef]
- Eloy, J.O.; Petrilli, R.; Trevizan, L.N.F.; Chorilli, M. Immunoliposomes: A review on functionalization strategies and targets for drug delivery. Colloids Surf. B Biointerfaces 2017, 159, 454–467. [Google Scholar] [CrossRef] [Green Version]
- Suk, J.S.; Xu, Q.; Kim, N.; Hanes, J.; Ensign, L.M. PEGylation as a strategy for improving nanoparticle-based drug and gene delivery. Adv. Drug Deliv. Rev. 2016, 99, 28–51. [Google Scholar] [CrossRef] [Green Version]
- Smyth, T.; Kullberg, M.; Malik, N.; Smith-Jones, P.; Graner, M.W.; Anchordoquy, T.J. Biodistribution and delivery efficiency of unmodified tumor-derived exosomes. J. Control Release 2015, 199, 145–155. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Szebeni, J.; Bedőcs, P.; Rozsnyay, Z.; Weiszhár, Z.; Urbanics, R.; Rosivall, L.; Cohen, R.; Garbuzenko, O.; Báthori, G.; Tóth, M.; et al. Liposome-induced complement activation and related cardiopulmonary distress in pigs: Factors promoting reactogenicity of Doxil and AmBisome. Nanomed. Nanotechnol. Biol. Med. 2012, 8, 176–184. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kowalski, P.S.; Rudra, A.; Miao, L.; Anderson, D.G. Delivering the Messenger: Advances in Technologies for Therapeutic mRNA Delivery. Mol. Ther. 2019, 27, 710–728. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hou, X.; Zaks, T.; Langer, R.; Dong, Y. Lipid nanoparticles for mRNA delivery. Nat. Rev. Mater. 2021, 6, 1078–1094. [Google Scholar] [CrossRef] [PubMed]
- Makadia, H.K.; Siegel, S.J. Poly Lactic-co-Glycolic Acid (PLGA) as Biodegradable Controlled Drug Delivery Carrier. Polymers 2011, 3, 1377–1397. [Google Scholar] [CrossRef]
- Song, E.; Gaudin, A.; King, A.R.; Seo, Y.E.; Suh, H.W.; Deng, Y.; Cui, J.; Tietjen, G.T.; Huttner, A.; Saltzman, W.M. Surface chemistry governs cellular tropism of nanoparticles in the brain. Nat. Commun. 2017, 8, 15322. [Google Scholar] [CrossRef] [Green Version]
- Banstola, A.; Duwa, R.; Emami, F.; Jeong, J.-H.; Yook, S. Enhanced Caspase-Mediated Abrogation of Autophagy by Temozolomide-Loaded and Panitumumab-Conjugated Poly(lactic-co-glycolic acid) Nanoparticles in Epidermal Growth Factor Receptor Overexpressing Glioblastoma Cells. Mol. Pharm. 2020, 17, 4386–4400. [Google Scholar] [CrossRef]
- Jackson, C.L.; Chanzy, H.D.; Booy, F.P.; Drake, B.J.; Tomalia, D.A.; Bauer, B.J.; Amis, E.J. Visualization of Dendrimer Molecules by Transmission Electron Microscopy (TEM): Staining Methods and Cryo-TEM of Vitrified Solutions. Macromolecules 1998, 31, 6259–6265. [Google Scholar] [CrossRef]
- Zielińska, A.; Carreiró, F.; Oliveira, A.M.; Neves, A.; Pires, B.; Venkatesh, D.N.; Durazzo, A.; Lucarini, M.; Eder, P.; Silva, A.M.; et al. Polymeric Nanoparticles: Production, Characterization, Toxicology and Ecotoxicology. Molecules 2020, 25, 3731. [Google Scholar] [CrossRef]
- Lim, J.-M.; Cai, T.; Mandaric, S.; Chopra, S.; Han, H.; Jang, S.; Il Choi, W.; Langer, R.; Farokhzad, O.C.; Karnik, R. Drug loading augmentation in polymeric nanoparticles using a coaxial turbulent jet mixer: Yong investigator perspective. J. Colloid Interface Sci. 2019, 538, 45–50. [Google Scholar] [CrossRef]
- Gref, R.; Minamitake, Y.; Peracchia, M.T.; Trubetskoy, V.; Torchilin, V.; Langer, R. Biodegradable Long-Circulating Polymeric Nanospheres. Science 1994, 263, 1600–1603. [Google Scholar] [CrossRef] [Green Version]
- Hu, X.; Zhang, Y.; Ding, T.; Liu, J.; Zhao, H. Multifunctional Gold Nanoparticles: A Novel Nanomaterial for Various Medical Applications and Biological Activities. Front. Bioeng. Biotechnol. 2020, 8, 990. [Google Scholar] [CrossRef] [PubMed]
- Sababathy, M.; Ramanathan, G.; Tan, S.C. Targeted delivery of gold nanoparticles by neural stem cells to glioblastoma for enhanced radiation therapy: A review. AIMS Neurosci. 2022, 9, 303–319. [Google Scholar] [CrossRef] [PubMed]
- Arias, L.; Pessan, J.; Vieira, A.; Lima, T.; Delbem, A.; Monteiro, D. Iron Oxide Nanoparticles for Biomedical Applications: A Perspective on Synthesis, Drugs, Antimicrobial Activity, and Toxicity. Antibiotics 2018, 7, 46. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Najahi-Missaoui, W.; Arnold, R.D.; Cummings, B.S. Safe Nanoparticles: Are We There Yet? Int. J. Mol. Sci. 2020, 22, 385. [Google Scholar] [CrossRef]
- Alshehri, R.; Ilyas, A.M.; Hasan, A.; Arnaout, A.; Ahmed, F.; Memic, A. Carbon Nanotubes in Biomedical Applications: Factors, Mechanisms, and Remedies of Toxicity. J. Med. Chem. 2016, 59, 8149–8167. [Google Scholar] [CrossRef]
- Hoshino, A.; Costa-Silva, B.; Shen, T.L.; Rodrigues, G.; Hashimoto, A.; Tesic Mark, M.; Molina, H.; Kohsaka, S.; Di Giannatale, A.; Ceder, S.; et al. Tumour exosome integrins determine organotropic metastasis. Nature 2015, 527, 329–335. [Google Scholar] [CrossRef] [Green Version]
- Antimisiaris, S.G.; Mourtas, S.; Marazioti, A. Exosomes and Exosome-Inspired Vesicles for Targeted Drug Delivery. Pharmaceutics 2018, 10, 218. [Google Scholar] [CrossRef] [Green Version]
- Saleh, A.F.; Lázaro-Ibáñez, E.; Forsgard, M.A.-M.; Shatnyeva, O.; Osteikoetxea, X.; Karlsson, F.; Heath, N.; Ingelsten, M.; Rose, J.; Harris, J.; et al. Extracellular vesicles induce minimal hepatotoxicity and immunogenicity. Nanoscale 2019, 11, 6990–7001. [Google Scholar] [CrossRef]
- Zhu, X.; Badawi, M.; Pomeroy, S.; Sutaria, D.S.; Xie, Z.; Baek, A.; Jiang, J.; Elgamal, O.A.; Mo, X.; Perle, K.L.; et al. Comprehensive toxicity and immunogenicity studies reveal minimal effects in mice following sustained dosing of extracellular vesicles derived from HEK293T cells. J. Extracell. Vesicles 2017, 6, 1324730. [Google Scholar] [CrossRef] [Green Version]
- Imai, T.; Takahashi, Y.; Nishikawa, M.; Kato, K.; Morishita, M.; Yamashita, T.; Matsumoto, A.; Charoenviriyakul, C.; Takakura, Y. Macrophage-dependent clearance of systemically administered B16BL6-derived exosomes from the blood circulation in mice. J. Extracell. Vesicles 2015, 4, 26238. [Google Scholar] [CrossRef]
- Mondal, J.; Pillarisetti, S.; Junnuthula, V.; Saha, M.; Hwang, S.R.; Park, I.K.; Lee, Y.K. Hybrid exosomes, exosome-like nanovesicles and engineered exosomes for therapeutic applications. J. Control Release 2022, 353, 1127–1149. [Google Scholar] [CrossRef] [PubMed]
- Gurung, S.; Perocheau, D.; Touramanidou, L.; Baruteau, J. The exosome journey: From biogenesis to uptake and intracellular signalling. Cell Commun. Signal. 2021, 19, 47. [Google Scholar] [CrossRef] [PubMed]
- Gauro, R.; Nandave, M.; Jain, V.K.; Jain, K. Advances in dendrimer-mediated targeted drug delivery to the brain. J. Nanopart. Res. 2021, 23, 76. [Google Scholar] [CrossRef]
- Sajid, M.I.; Jamshaid, U.; Jamshaid, T.; Zafar, N.; Fessi, H.; Elaissari, A. Carbon nanotubes from synthesis to in vivo biomedical applications. Int. J. Pharm. 2016, 501, 278–299. [Google Scholar] [CrossRef] [PubMed]
- Pednekar, P.P.; Godiyal, S.C.; Jadhav, K.R.; Kadam, V.J. Chapter 23—Mesoporous silica nanoparticles: A promising multifunctional drug delivery system. In Nanostructures for Cancer Therapy; Ficai, A., Grumezescu, A.M., Eds.; Elsevier: Amsterdam, The Netherlands, 2017; pp. 593–621. [Google Scholar]
- Bharti, C.; Gulati, N.; Nagaich, U.; Pal, A. Mesoporous silica nanoparticles in target drug delivery system: A review. Int. J. Pharm. Investig. 2015, 5, 124. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Akbarzadeh, A.; Rezaei-Sadabady, R.; Davaran, S.; Joo, S.W.; Zarghami, N.; Hanifehpour, Y.; Samiei, M.; Kouhi, M.; Nejati-Koshki, K. Liposome: Classification, preparation, and applications. Nanoscale Res. Lett. 2013, 8, 102. [Google Scholar] [CrossRef] [Green Version]
- Gregoriadis, G.; Ryman, B.E. Fate of Protein-Containing Liposomes Injected into Rats. An Approach to the Treatment of Storage Diseases. Eur. J. Biochem. 1972, 24, 485–491. [Google Scholar] [CrossRef]
- Mohamed, M.; Abu Lila, A.S.; Shimizu, T.; Alaaeldin, E.; Hussein, A.; Sarhan, H.A.; Szebeni, J.; Ishida, T. PEGylated liposomes: Immunological responses. Sci. Technol. Adv. Mater. 2019, 20, 710–724. [Google Scholar] [CrossRef] [Green Version]
- Kulkarni, J.A.; Witzigmann, D.; Leung, J.; Tam, Y.Y.C.; Cullis, P.R. On the role of helper lipids in lipid nanoparticle formulations of siRNA. Nanoscale 2019, 11, 21733–21739. [Google Scholar] [CrossRef]
- Natarajan, J.; Baskaran, M.; Humtsoe, L.C.; Vadivelan, R.; Justin, A. Enhanced brain targeting efficacy of Olanzapine through solid lipid nanoparticles. Artif. Cells Nanomed. Biotechnol. 2017, 45, 364–371. [Google Scholar] [CrossRef] [Green Version]
- Pashirova, T.N.; Zueva, I.V.; Petrov, K.A.; Babaev, V.M.; Lukashenko, S.S.; Rizvanov, I.K.; Souto, E.B.; Nikolsky, E.E.; Zakharova, L.Y.; Masson, P.; et al. Nanoparticle-Delivered 2-PAM for Rat Brain Protection against Paraoxon Central Toxicity. ACS Appl. Mater. Interfaces 2017, 9, 16922–16932. [Google Scholar] [CrossRef] [PubMed]
- Mitchell, M.J.; Billingsley, M.M.; Haley, R.M.; Wechsler, M.E.; Peppas, N.A.; Langer, R. Engineering precision nanoparticles for drug delivery. Nat. Rev. Drug Discov. 2021, 20, 101–124. [Google Scholar] [CrossRef] [PubMed]
- Jaiswal, M.; Dudhe, R.; Sharma, P.K. Nanoemulsion: An advanced mode of drug delivery system. 3 Biotech 2015, 5, 123–127. [Google Scholar] [CrossRef] [Green Version]
- Carvalho, V.F.M.; Salata, G.C.; de Matos, J.K.R.; Costa-Fernandez, S.; Chorilli, M.; Steiner, A.A.; de Araujo, G.L.B.; Silveira, E.R.; Costa-Lotufo, L.V.; Lopes, L.B. Optimization of composition and obtainment parameters of biocompatible nanoemulsions intended for intraductal administration of piplartine (piperlongumine) and mammary tissue targeting. Int. J. Pharm. 2019, 567, 118460. [Google Scholar] [CrossRef] [PubMed]
- Sánchez-López, E.; Guerra, M.; Dias-Ferreira, J.; Lopez-Machado, A.; Ettcheto, M.; Cano, A.; Espina, M.; Camins, A.; Garcia, M.L.; Souto, E.B. Current Applications of Nanoemulsions in Cancer Therapeutics. Nanomaterials 2019, 9, 821. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Choudhury, H.; Gorain, B.; Karmakar, S.; Biswas, E.; Dey, G.; Barik, R.; Mandal, M.; Pal, T.K. Improvement of cellular uptake, in vitro antitumor activity and sustained release profile with increased bioavailability from a nanoemulsion platform. Int. J. Pharm. 2014, 460, 131–143. [Google Scholar] [CrossRef] [PubMed]
- Gadhave, D.; Gorain, B.; Tagalpallewar, A.; Kokare, C. Intranasal teriflunomide microemulsion: An improved chemotherapeutic approach in glioblastoma. J. Drug Deliv. Sci. Technol. 2019, 51, 276–289. [Google Scholar] [CrossRef]
- Shinde, R.L.; Devarajan, P.V. Docosahexaenoic acid–mediated, targeted and sustained brain delivery of curcumin microemulsion. Drug Deliv. 2017, 24, 152–161. [Google Scholar] [CrossRef] [Green Version]
- Bonferoni, M.; Rossi, S.; Sandri, G.; Ferrari, F.; Gavini, E.; Rassu, G.; Giunchedi, P. Nanoemulsions for “Nose-to-Brain” Drug Delivery. Pharmaceutics 2019, 11, 84. [Google Scholar] [CrossRef] [Green Version]
- Shieh, L.; Tamada, J.; Chen, I.; Pang, J.; Domb, A.; Langer, R. Erosion of a new family of biodegradable polyanhydrides. J. Biomed. Mater. Res. 1994, 28, 1465–1475. [Google Scholar] [CrossRef]
- Tabata, Y.; Langer, R. Polyanhydride microspheres that display near-constant release of water-soluble model drug compounds. Pharm. Res. 1993, 10, 391–399. [Google Scholar] [CrossRef] [PubMed]
- Jain, J.P.; Modi, S.; Kumar, N. Hydroxy fatty acid based polyanhydride as drug delivery system: Synthesis, characterization, in vitro degradation, drug release, and biocompatibility. J. Biomed. Mater. Res. A 2008, 84, 740–752. [Google Scholar] [CrossRef] [PubMed]
- Deng, Y.; Saucier-Sawyer, J.K.; Hoimes, C.J.; Zhang, J.; Seo, Y.E.; Andrejecsk, J.W.; Saltzman, W.M. The effect of hyperbranched polyglycerol coatings on drug delivery using degradable polymer nanoparticles. Biomaterials 2014, 35, 6595–6602. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Eivazi, N.; Rahmani, R.; Paknejad, M. Specific cellular internalization and pH-responsive behavior of doxorubicin loaded PLGA-PEG nanoparticles targeted with anti EGFRvIII antibody. Life Sci. 2020, 261, 118361. [Google Scholar] [CrossRef]
- Gagliardi, A.; Giuliano, E.; Venkateswararao, E.; Fresta, M.; Bulotta, S.; Awasthi, V.; Cosco, D. Biodegradable Polymeric Nanoparticles for Drug Delivery to Solid Tumors. Front. Pharmacol. 2021, 12, 601626. [Google Scholar] [CrossRef]
- Wang, W.; Meng, Q.; Li, Q.; Liu, J.; Zhou, M.; Jin, Z.; Zhao, K. Chitosan Derivatives and Their Application in Biomedicine. Int. J. Mol. Sci. 2020, 21, 487. [Google Scholar] [CrossRef] [Green Version]
- Cheng, J.; Teply, B.; Sherifi, I.; Sung, J.; Luther, G.; Gu, F.; Levynissenbaum, E.; Radovicmoreno, A.; Langer, R.; Farokhzad, O. Formulation of functionalized PLGA–PEG nanoparticles for in vivo targeted drug delivery. Biomaterials 2007, 28, 869–876. [Google Scholar] [CrossRef] [Green Version]
- Allyn, M.M.; Luo, R.H.; Hellwarth, E.B.; Swindle-Reilly, K.E. Considerations for Polymers Used in Ocular Drug Delivery. Front. Med. 2021, 8, 787644. [Google Scholar] [CrossRef]
- Huntimer, L.; Ramer-Tait, A.E.; Petersen, L.K.; Ross, K.A.; Walz, K.A.; Wang, C.; Hostetter, J.; Narasimhan, B.; Wannemuehler, M.J. Evaluation of biocompatibility and administration site reactogenicity of polyanhydride-particle-based platform for vaccine delivery. Adv. Healthc. Mater. 2013, 2, 369–378. [Google Scholar] [CrossRef]
- Vela-Ramirez, J.E.; Goodman, J.T.; Boggiatto, P.M.; Roychoudhury, R.; Pohl, N.L.B.; Hostetter, J.M.; Wannemuehler, M.J.; Narasimhan, B. Safety and Biocompatibility of Carbohydrate-Functionalized Polyanhydride Nanoparticles. AAPS J. 2015, 17, 256–267. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Choi, J.; Rui, Y.; Kim, J.; Gorelick, N.; Wilson, D.R.; Kozielski, K.; Mangraviti, A.; Sankey, E.; Brem, H.; Tyler, B.; et al. Nonviral polymeric nanoparticles for gene therapy in pediatric CNS malignancies. Nanomedicine 2020, 23, 102115. [Google Scholar] [CrossRef] [PubMed]
- Madej, M.; Kurowska, N.; Strzalka-Mrozik, B. Polymeric Nanoparticles—Tools in a Drug Delivery System in Selected Cancer Therapies. Appl. Sci. 2022, 12, 9479. [Google Scholar] [CrossRef]
- Wang, Y.; Hu, A. Carbon quantum dots: Synthesis, properties and applications. J. Mater. Chem. C 2014, 2, 6921. [Google Scholar] [CrossRef] [Green Version]
- Kushwaha, S.K.S.; Ghoshal, S.; Rai, A.K.; Singh, S. Carbon nanotubes as a novel drug delivery system for anticancer therapy: A review. Braz. J. Pharm. Sci. 2013, 49, 629–643. [Google Scholar] [CrossRef] [Green Version]
- Valadi, H.; Ekström, K.; Bossios, A.; Sjöstrand, M.; Lee, J.J.; Lötvall, J.O. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat. Cell Biol. 2007, 9, 654–659. [Google Scholar] [CrossRef] [Green Version]
- Peters, P.J.; Geuze, H.J.; Van Donk, H.A.D.; Slot, J.W.; Griffith, J.M.; Stam, N.J.; Clevers, H.C.; Borst, J. Molecules relevant for T cell-target cell interaction are present in cytolytic granules of human T lymphocytes. Eur. J. Immunol. 1989, 19, 1469–1475. [Google Scholar] [CrossRef] [Green Version]
- van Niel, G.; Raposo, G.; Candalh, C.; Boussac, M.; Hershberg, R.; Cerf-Bensussan, N.; Heyman, M. Intestinal epithelial cells secrete exosome-like vesicles. Gastroenterology 2001, 121, 337–349. [Google Scholar] [CrossRef]
- Raposo, G.; Nijman, H.W.; Stoorvogel, W.; Liejendekker, R.; Harding, C.V.; Melief, C.J.; Geuze, H.J. B lymphocytes secrete antigen-presenting vesicles. J. Exp. Med. 1996, 183, 1161–1172. [Google Scholar] [CrossRef]
- Raposo, G.; Tenza, D.; Mecheri, S.; Peronet, R.; Bonnerot, C.; Desaymard, C. Accumulation of Major Histocompatibility Complex Class II Molecules in Mast Cell Secretory Granules and Their Release upon Degranulation. Mol. Biol. Cell 1997, 8, 2631–2645. [Google Scholar] [CrossRef] [Green Version]
- Wolfers, J.; Lozier, A.; Raposo, G.; Regnault, A.; Théry, C.; Masurier, C.; Flament, C.; Pouzieux, S.; Faure, F.; Tursz, T.; et al. Tumor-derived exosomes are a source of shared tumor rejection antigens for CTL cross-priming. Nat. Med. 2001, 7, 297–303. [Google Scholar] [CrossRef] [PubMed]
- Zitvogel, L.; Regnault, A.; Lozier, A.; Wolfers, J.; Flament, C.; Tenza, D.; Ricciardi-Castagnoli, P.; Raposo, G.; Amigorena, S. Eradication of established murine tumors using a novel cell-free vaccine: Dendritic cell derived exosomes. Nat. Med. 1998, 4, 594–600. [Google Scholar] [CrossRef] [PubMed]
- Heijnen, H.F.; Schiel, A.E.; Fijnheer, R.; Geuze, H.J.; Sixma, J.J. Activated platelets release two types of membrane vesicles: Microvesicles by surface shedding and exosomes derived from exocytosis of multivesicular bodies and alpha-granules. Blood 1999, 94, 3791–3799. [Google Scholar] [CrossRef] [PubMed]
- Zheng, Y.; Tu, C.; Zhang, J.; Wang, J. Inhibition of multiple myeloma-derived exosomes uptake suppresses the functional response in bone marrow stromal cell. Int. J. Oncol. 2019, 54, 1061–1070. [Google Scholar] [CrossRef] [Green Version]
- Wen, S.W.; Lima, L.G.; Lobb, R.J.; Norris, E.L.; Hastie, M.L.; Krumeich, S.; Moller, A. Breast Cancer-Derived Exosomes Reflect the Cell-of-Origin Phenotype. Proteomics 2019, 19, e1800180. [Google Scholar] [CrossRef] [PubMed]
- Andriolo, G.; Provasi, E.; Lo Cicero, V.; Brambilla, A.; Soncin, S.; Torre, T.; Milano, G.; Biemmi, V.; Vassalli, G.; Turchetto, L.; et al. Exosomes From Human Cardiac Progenitor Cells for Therapeutic Applications: Development of a GMP-Grade Manufacturing Method. Front. Physiol. 2018, 9, 1169. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yuan, D.; Zhao, Y.; Banks, W.A.; Bullock, K.M.; Haney, M.; Batrakova, E.; Kabanov, A.V. Macrophage exosomes as natural nanocarriers for protein delivery to inflamed brain. Biomaterials 2017, 142, 1–12. [Google Scholar] [CrossRef] [PubMed]
- Yu, B.; Zhang, X.; Li, X. Exosomes Derived from Mesenchymal Stem Cells. Int. J. Mol. Sci. 2014, 15, 4142–4157. [Google Scholar] [CrossRef] [Green Version]
- Wan, R.; Hussain, A.; Behfar, A.; Moran, S.L.; Zhao, C. The Therapeutic Potential of Exosomes in Soft Tissue Repair and Regeneration. Int. J. Mol. Sci. 2022, 23, 3869. [Google Scholar] [CrossRef]
- Liu, J.; Chen, Y.; Pei, F.; Zeng, C.; Yao, Y.; Liao, W.; Zhao, Z. Extracellular Vesicles in Liquid Biopsies: Potential for Disease Diagnosis. BioMed Res. Int. 2021, 2021, 6611244. [Google Scholar] [CrossRef]
- García-Romero, N.; Carrión-Navarro, J.; Esteban-Rubio, S.; Lázaro-Ibáñez, E.; Peris-Celda, M.; Alonso, M.M.; Guzmán-De-Villoria, J.; Fernández-Carballal, C.; De Mendivil, A.O.; García-Duque, S.; et al. DNA sequences within glioma-derived extracellular vesicles can cross the intact blood-brain barrier and be detected in peripheral blood of patients. Oncotarget 2017, 8, 1416–1428. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Théry, C.; Witwer, K.W.; Aikawa, E.; Alcaraz, M.J.; Anderson, J.D.; Andriantsitohaina, R.; Antoniou, A.; Arab, T.; Archer, F.; Atkin-Smith, G.K.; et al. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): A position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. J. Extracell. Vesicles 2018, 7, 1535750. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Johnstone, R.M.; Adam, M.; Hammond, J.R.; Orr, L.; Turbide, C. Vesicle formation during reticulocyte maturation. Association of plasma membrane activities with released vesicles (exosomes). J. Biol. Chem. 1987, 262, 9412–9420. [Google Scholar] [CrossRef] [PubMed]
- Men, Y.; Yelick, J.; Jin, S.; Tian, Y.; Chiang, M.S.R.; Higashimori, H.; Brown, E.; Jarvis, R.; Yang, Y. Exosome reporter mice reveal the involvement of exosomes in mediating neuron to astroglia communication in the CNS. Nat. Commun. 2019, 10, 4136. [Google Scholar] [CrossRef] [Green Version]
- Nolte-’t Hoen, E.N.; Buschow, S.I.; Anderton, S.M.; Stoorvogel, W.; Wauben, M.H. Activated T cells recruit exosomes secreted by dendritic cells via LFA-1. Blood 2009, 113, 1977–1981. [Google Scholar] [CrossRef] [Green Version]
- Zhang, B.; Wang, M.; Gong, A.; Zhang, X.; Wu, X.; Zhu, Y.; Shi, H.; Wu, L.; Zhu, W.; Qian, H.; et al. HucMSC-Exosome Mediated-Wnt4 Signaling Is Required for Cutaneous Wound Healing. Stem Cells 2015, 33, 2158–2168. [Google Scholar] [CrossRef]
- Osaki, M.; Okada, F. Exosomes and Their Role in Cancer Progression. Yonago Acta Med. 2019, 62, 182–190. [Google Scholar] [CrossRef] [Green Version]
- Bang, C.; Batkai, S.; Dangwal, S.; Gupta, S.K.; Foinquinos, A.; Holzmann, A.; Just, A.; Remke, J.; Zimmer, K.; Zeug, A.; et al. Cardiac fibroblast–derived microRNA passenger strand-enriched exosomes mediate cardiomyocyte hypertrophy. J. Clin. Investig. 2014, 124, 2136–2146. [Google Scholar] [CrossRef] [Green Version]
- Howitt, J.; Hill, A.F. Exosomes in the Pathology of Neurodegenerative Diseases. J. Biol. Chem. 2016, 291, 26589–26597. [Google Scholar] [CrossRef] [Green Version]
- Al-Nedawi, K.; Meehan, B.; Micallef, J.; Lhotak, V.; May, L.; Guha, A.; Rak, J. Intercellular transfer of the oncogenic receptor EGFRvIII by microvesicles derived from tumour cells. Nat. Cell Biol. 2008, 10, 619–624. [Google Scholar] [CrossRef]
- Thery, C.; Boussac, M.; Veron, P.; Ricciardi-Castagnoli, P.; Raposo, G.; Garin, J.; Amigorena, S. Proteomic analysis of dendritic cell-derived exosomes: A secreted subcellular compartment distinct from apoptotic vesicles. J. Immunol. 2001, 166, 7309–7318. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Blanchard, N.; Lankar, D.; Faure, F.; Regnault, A.; Dumont, C.; Raposo, G.; Hivroz, C. TCR activation of human T cells induces the production of exosomes bearing the TCR/CD3/zeta complex. J. Immunol. 2002, 168, 3235–3241. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Clayton, A.; Court, J.; Navabi, H.; Adams, M.; Mason, M.D.; Hobot, J.A.; Newman, G.R.; Jasani, B. Analysis of antigen presenting cell derived exosomes, based on immuno-magnetic isolation and flow cytometry. J. Immunol. Methods 2001, 247, 163–174. [Google Scholar] [CrossRef]
- Théry, C.; Zitvogel, L.; Amigorena, S. Exosomes: Composition, biogenesis and function. Nat. Rev. Immunol. 2002, 2, 569–579. [Google Scholar] [CrossRef] [PubMed]
- Skotland, T.; Sandvig, K.; Llorente, A. Lipids in exosomes: Current knowledge and the way forward. Prog. Lipid Res. 2017, 66, 30–41. [Google Scholar] [CrossRef]
- Théry, C.; Duban, L.; Segura, E.; Véron, P.; Lantz, O.; Amigorena, S. Indirect activation of naïve CD4+ T cells by dendritic cell–derived exosomes. Nat. Immunol. 2002, 3, 1156–1162. [Google Scholar] [CrossRef]
- Charoenviriyakul, C.; Takahashi, Y.; Morishita, M.; Nishikawa, M.; Takakura, Y. Role of Extracellular Vesicle Surface Proteins in the Pharmacokinetics of Extracellular Vesicles. Mol. Pharm. 2018, 15, 1073–1080. [Google Scholar] [CrossRef]
- Huang, X.; Yuan, T.; Tschannen, M.; Sun, Z.; Jacob, H.; Du, M.; Liang, M.; Dittmar, R.L.; Liu, Y.; Liang, M.; et al. Characterization of human plasma-derived exosomal RNAs by deep sequencing. BMC Genom. 2013, 14, 319. [Google Scholar] [CrossRef] [Green Version]
- Kooijmans, S.A.A.; Aleza, C.G.; Roffler, S.R.; Van Solinge, W.W.; Vader, P.; Schiffelers, R.M. Display of GPI-anchored anti-EGFR nanobodies on extracellular vesicles promotes tumour cell targeting. J. Extracell. Vesicles 2016, 5, 31053. [Google Scholar] [CrossRef] [Green Version]
- Kooijmans, S.A.A.; Fliervoet, L.A.L.; van der Meel, R.; Fens, M.; Heijnen, H.F.G.; van Bergen En Henegouwen, P.M.P.; Vader, P.; Schiffelers, R.M. PEGylated and targeted extracellular vesicles display enhanced cell specificity and circulation time. J. Control Release 2016, 224, 77–85. [Google Scholar] [CrossRef]
- Kamerkar, S.; Lebleu, V.S.; Sugimoto, H.; Yang, S.; Ruivo, C.F.; Melo, S.A.; Lee, J.J.; Kalluri, R. Exosomes facilitate therapeutic targeting of oncogenic KRAS in pancreatic cancer. Nature 2017, 546, 498–503. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Murphy, D.E.; de Jong, O.G.; Brouwer, M.; Wood, M.J.; Lavieu, G.; Schiffelers, R.M.; Vader, P. Extracellular vesicle-based therapeutics: Natural versus engineered targeting and trafficking. Exp. Mol. Med. 2019, 51, 1–12. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lázaro-Ibáñez, E.; Faruqu, F.N.; Saleh, A.F.; Silva, A.M.; Tzu-Wen Wang, J.; Rak, J.; Al-Jamal, K.T.; Dekker, N. Selection of Fluorescent, Bioluminescent, and Radioactive Tracers to Accurately Reflect Extracellular Vesicle Biodistribution in Vivo. ACS Nano 2021, 15, 3212–3227. [Google Scholar] [CrossRef] [PubMed]
- Goh, W.J.; Zou, S.; Ong, W.Y.; Torta, F.; Alexandra, A.F.; Schiffelers, R.M.; Storm, G.; Wang, J.-W.; Czarny, B.; Pastorin, G. Bioinspired Cell-Derived Nanovesicles versus Exosomes as Drug Delivery Systems: A Cost-Effective Alternative. Sci. Rep. 2017, 7, 14322. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wen, Y.; Fu, Q.; Soliwoda, A.; Zhang, S.; Zheng, M.; Mao, W.; Wan, Y. Cell-derived nanovesicles prepared by membrane extrusion are good substitutes for natural extracellular vesicles. Extracell. Vesicle 2022, 1, 100004. [Google Scholar] [CrossRef]
- Jang, S.C.; Kim, O.Y.; Yoon, C.M.; Choi, D.-S.; Roh, T.-Y.; Park, J.; Nilsson, J.; Lötvall, J.; Kim, Y.-K.; Gho, Y.S. Bioinspired Exosome-Mimetic Nanovesicles for Targeted Delivery of Chemotherapeutics to Malignant Tumors. ACS Nano 2013, 7, 7698–7710. [Google Scholar] [CrossRef]
- Goh, W.J.; Lee, C.K.; Zou, S.; Woon, E.; Czarny, B.; Pastorin, G. Doxorubicin-loaded cell-derived nanovesicles: An alternative targeted approach for anti-tumor therapy. Int. J. Nanomed. 2017, 12, 2759–2767. [Google Scholar] [CrossRef] [Green Version]
- Wilhelm, S.; Tavares, A.J.; Dai, Q.; Ohta, S.; Audet, J.; Dvorak, H.F.; Chan, W.C.W. Analysis of nanoparticle delivery to tumours. Nat. Rev. Mater. 2016, 1, 16014. [Google Scholar] [CrossRef]
- Sun, C.; Ding, Y.; Zhou, L.; Shi, D.; Sun, L.; Webster, T.J.; Shen, Y. Noninvasive nanoparticle strategies for brain tumor targeting. Nanomedicine 2017, 13, 2605–2621. [Google Scholar] [CrossRef]
- Li, J.; Zhao, J.; Tan, T.; Liu, M.; Zeng, Z.; Zeng, Y.; Zhang, L.; Fu, C.; Chen, D.; Xie, T. Nanoparticle Drug Delivery System for Glioma and Its Efficacy Improvement Strategies: A Comprehensive Review. Int. J. Nanomed. 2020, 15, 2563–2582. [Google Scholar] [CrossRef] [Green Version]
- Hwang, D.W.; Choi, H.; Jang, S.C.; Yoo, M.Y.; Park, J.Y.; Choi, N.E.; Oh, H.J.; Ha, S.; Lee, Y.-S.; Jeong, J.M.; et al. Noninvasive imaging of radiolabeled exosome-mimetic nanovesicle using 99mTc-HMPAO. Sci. Rep. 2015, 5, 15636. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Klibanov, A.L.; Maruyama, K.; Torchilin, V.P.; Huang, L. Amphipathic Polyethyleneglycols Effectively Prolong the Circulation Time of Liposomes. FEBS Lett. 1990, 268, 235–237. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hennig, R.; Pollinger, K.; Veser, A.; Breunig, M.; Goepferich, A. Nanoparticle multivalency counterbalances the ligand affinity loss upon PEGylation. J. Control Release 2014, 194, 20–27. [Google Scholar] [CrossRef] [PubMed]
- Nunes, S.S.; De Oliveira Silva, J.; Fernandes, R.S.; Miranda, S.E.M.; Leite, E.A.; De Farias, M.A.; Portugal, R.V.; Cassali, G.D.; Townsend, D.M.; Oliveira, M.C.; et al. PEGylated versus Non-PEGylated pH-Sensitive Liposomes: New Insights from a Comparative Antitumor Activity Study. Pharmaceutics 2022, 14, 272. [Google Scholar] [CrossRef] [PubMed]
- Frank, T.; Klinker, F.; Falkenburger, B.H.; Laage, R.; Lühder, F.; Göricke, B.; Schneider, A.; Neurath, H.; Desel, H.; Liebetanz, D.; et al. Pegylated granulocyte colony-stimulating factor conveys long-term neuroprotection and improves functional outcome in a model of Parkinson’s disease. Brain 2012, 135, 1914–1925. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Elinav, E.; Niv-Spector, L.; Katz, M.; Price, T.O.; Ali, M.; Yacobovitz, M.; Solomon, G.; Reicher, S.; Lynch, J.L.; Halpern, Z.; et al. Pegylated leptin antagonist is a potent orexigenic agent: Preparation and mechanism of activity. Endocrinology 2009, 150, 3083–3091. [Google Scholar] [CrossRef] [Green Version]
- Yang, Q.; Lai, S.K. Anti-PEG immunity: Emergence, characteristics, and unaddressed questions. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol. 2015, 7, 655–677. [Google Scholar] [CrossRef] [Green Version]
- Chao, M.P.; Weissman, I.L.; Majeti, R. The CD47–SIRPα pathway in cancer immune evasion and potential therapeutic implications. Curr. Opin. Immunol. 2012, 24, 225–232. [Google Scholar] [CrossRef] [Green Version]
- Belhadj, Z.; He, B.; Deng, H.; Song, S.; Zhang, H.; Wang, X.; Dai, W.; Zhang, Q. A combined “eat me/don't eat me” strategy based on extracellular vesicles for anticancer nanomedicine. J. Extracell. Vesicles 2020, 9, 1806444. [Google Scholar] [CrossRef]
- Rodriguez, P.L.; Harada, T.; Christian, D.A.; Pantano, D.A.; Tsai, R.K.; Discher, D.E. Minimal "Self" Peptides That Inhibit Phagocytic Clearance and Enhance Delivery of Nanoparticles. Science 2013, 339, 971–975. [Google Scholar] [CrossRef] [Green Version]
- Hayat, S.M.G.; Jaafari, M.R.; Hatamipour, M.; Penson, P.E.; Sahebkar, A. Liposome Circulation Time is Prolonged by CD47 Coating. Protein Pept. Lett. 2020, 27, 1029–1037. [Google Scholar] [CrossRef] [PubMed]
- Yu, M.; Zheng, J. Clearance Pathways and Tumor Targeting of Imaging Nanoparticles. ACS Nano 2015, 9, 6655–6674. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhang, W.; Mehta, A.; Tong, Z.; Esser, L.; Voelcker, N.H. Development of Polymeric Nanoparticles for Blood–Brain Barrier Transfer—Strategies and Challenges. Adv. Sci. 2021, 8, 2003937. [Google Scholar] [CrossRef] [PubMed]
- Juliano, R.L.; Stamp, D. The effect of particle size and charge on the clearance rates of liposomes and liposome encapsulated drugs. Biochem. Biophys. Res. Commun. 1975, 63, 651–658. [Google Scholar] [CrossRef] [PubMed]
- Zhang, F.; Trent Magruder, J.; Lin, Y.-A.; Crawford, T.C.; Grimm, J.C.; Sciortino, C.M.; Wilson, M.A.; Blue, M.E.; Kannan, S.; Johnston, M.V.; et al. Generation-6 hydroxyl PAMAM dendrimers improve CNS penetration from intravenous administration in a large animal brain injury model. J. Control Release 2017, 249, 173–182. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sonavane, G.; Tomoda, K.; Makino, K. Biodistribution of colloidal gold nanoparticles after intravenous administration: Effect of particle size. Colloids Surf. B Biointerfaces 2008, 66, 274–280. [Google Scholar] [CrossRef]
- Graham, D.K.; DeRyckere, D.; Davies, K.D.; Earp, H.S. The TAM family: Phosphatidylserine sensing receptor tyrosine kinases gone awry in cancer. Nat. Rev. Cancer 2014, 14, 769–785. [Google Scholar] [CrossRef]
- Matsumoto, A.; Takahashi, Y.; Nishikawa, M.; Sano, K.; Morishita, M.; Charoenviriyakul, C.; Saji, H.; Takakura, Y. Role of Phosphatidylserine-Derived Negative Surface Charges in the Recognition and Uptake of Intravenously Injected B16BL6-Derived Exosomes by Macrophages. J. Pharm. Sci. 2017, 106, 168–175. [Google Scholar] [CrossRef] [Green Version]
- Patel, H.M.; Tuzel, N.S.; Ryman, B.E. Inhibitory effect of cholesterol on the uptake of liposomes by liver and spleen. Biochim. Biophys. Acta (BBA)—Gen. Subj. 1983, 761, 142–151. [Google Scholar] [CrossRef]
- Champion, J.A.; Mitragotri, S. Role of target geometry in phagocytosis. Proc. Natl. Acad. Sci. USA 2006, 103, 4930–4934. [Google Scholar] [CrossRef] [Green Version]
- Huang, X.; Li, L.; Liu, T.; Hao, N.; Liu, H.; Chen, D.; Tang, F. The Shape Effect of Mesoporous Silica Nanoparticles on Biodistribution, Clearance, and Biocompatibility in Vivo. ACS Nano 2011, 5, 5390–5399. [Google Scholar] [CrossRef] [PubMed]
- Arnida;Janát-Amsbury, M.M.; Ray, A.; Peterson, C.M.; Ghandehari, H. Geometry and surface characteristics of gold nanoparticles influence their biodistribution and uptake by macrophages. Eur. J. Pharm. Biopharm. 2011, 77, 417–423. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yang, T.; Martin, P.; Fogarty, B.; Brown, A.; Schurman, K.; Phipps, R.; Yin, V.P.; Lockman, P.; Bai, S. Exosome Delivered Anticancer Drugs Across the Blood-Brain Barrier for Brain Cancer Therapy in Danio Rerio. Pharm. Res. 2015, 32, 2003–2014. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Na, J.H.; Koo, H.; Lee, S.; Min, K.H.; Park, K.; Yoo, H.; Lee, S.H.; Park, J.H.; Kwon, I.C.; Jeong, S.Y.; et al. Real-time and non-invasive optical imaging of tumor-targeting glycol chitosan nanoparticles in various tumor models. Biomaterials 2011, 32, 5252–5261. [Google Scholar] [CrossRef]
- Maksimenko, O.; Malinovskaya, J.; Shipulo, E.; Osipova, N.; Razzhivina, V.; Arantseva, D.; Yarovaya, O.; Mostovaya, U.; Khalansky, A.; Fedoseeva, V.; et al. Doxorubicin-loaded PLGA nanoparticles for the chemotherapy of glioblastoma: Towards the pharmaceutical development. Int. J. Pharm. 2019, 572, 118733. [Google Scholar] [CrossRef]
- Fang, C.; Wang, K.; Stephen, Z.R.; Mu, Q.; Kievit, F.M.; Chiu, D.T.; Press, O.W.; Zhang, M. Temozolomide Nanoparticles for Targeted Glioblastoma Therapy. ACS Appl. Mater. Interfaces 2015, 7, 6674–6682. [Google Scholar] [CrossRef] [Green Version]
- Marchetti, L.; Engelhardt, B. Immune cell trafficking across the blood-brain barrier in the absence and presence of neuroinflammation. Vasc. Biol. 2020, 2, H1–H18. [Google Scholar] [CrossRef] [Green Version]
- Liu, L.; Eckert, M.A.; Riazifar, H.; Kang, D.-K.; Agalliu, D.; Zhao, W. From Blood to the Brain: Can Systemically Transplanted Mesenchymal Stem Cells Cross the Blood-Brain Barrier? Stem Cells Int. 2013, 2013, 435093. [Google Scholar] [CrossRef]
- Cao, M.; Mao, J.; Duan, X.; Lu, L.; Zhang, F.; Lin, B.; Chen, M.; Zheng, C.; Zhang, X.; Shen, J. In vivo tracking of the tropism of mesenchymal stem cells to malignant gliomas using reporter gene-based MR imaging. Int. J. Cancer 2018, 142, 1033–1046. [Google Scholar] [CrossRef] [Green Version]
- Simionescu, M.; Ghinea, N.; Fixman, A.; Lasser, M.; Kukes, L.; Simionescu, N.; Palade, G.E. The cerebral microvasculature of the rat: Structure and luminal surface properties during early development. J. Submicrosc. Cytol. Pathol. 1988, 20, 243–261. [Google Scholar]
- Azarmi, M.; Maleki, H.; Nikkam, N.; Malekinejad, H. Transcellular brain drug delivery: A review on recent advancements. Int. J. Pharm. 2020, 586, 119582. [Google Scholar] [CrossRef] [PubMed]
- Moura, R.P.; Martins, C.; Pinto, S.; Sousa, F.; Sarmento, B. Blood-brain barrier receptors and transporters: An insight on their function and how to exploit them through nanotechnology. Expert Opin. Drug Deliv. 2019, 16, 271–285. [Google Scholar] [CrossRef]
- Moscariello, P.; Ng, D.Y.W.; Jansen, M.; Weil, T.; Luhmann, H.J.; Hedrich, J. Brain Delivery of Multifunctional Dendrimer Protein Bioconjugates. Adv. Sci. 2018, 5, 1700897. [Google Scholar] [CrossRef] [PubMed]
- Albertazzi, L.; Serresi, M.; Albanese, A.; Beltram, F. Dendrimer Internalization and Intracellular Trafficking in Living Cells. Mol. Pharm. 2010, 7, 680–688. [Google Scholar] [CrossRef] [PubMed]
- Ordóñez-Gutiérrez, L.; Re, F.; Bereczki, E.; Ioja, E.; Gregori, M.; Andersen, A.J.; Antón, M.; Moghimi, S.M.; Pei, J.-J.; Masserini, M.; et al. Repeated intraperitoneal injections of liposomes containing phosphatidic acid and cardiolipin reduce amyloid-β levels in APP/PS1 transgenic mice. Nanomed. Nanotechnol. Biol. Med. 2015, 11, 421–430. [Google Scholar] [CrossRef] [Green Version]
- Dehouck, B.; Fenart, L.; Dehouck, M.-P.; Pierce, A.; Torpier, G.; Cecchelli, R. A New Function for the LDL Receptor: Transcytosis of LDL across the Blood–Brain Barrier. J. Cell Biol. 1997, 138, 877–889. [Google Scholar] [CrossRef] [PubMed]
- Jefferies, W.A.; Brandon, M.R.; Hunt, S.V.; Williams, A.F.; Gatter, K.C.; Mason, D.Y. Transferrin receptor on endothelium of brain capillaries. Nature 1984, 312, 162–163. [Google Scholar] [CrossRef]
- Neves, A.R.; Queiroz, J.F.; Lima, S.A.C.; Reis, S. Apo E-Functionalization of Solid Lipid Nanoparticles Enhances Brain Drug Delivery: Uptake Mechanism and Transport Pathways. Bioconj. Chem. 2017, 28, 995–1004. [Google Scholar] [CrossRef]
- Hu, K.; Shi, Y.; Jiang, W.; Han, J.; Huang, S.; Jiang, X. Lactoferrin conjugated PEG-PLGA nanoparticles for brain delivery: Preparation, characterization and efficacy in Parkinson's disease. Int. J. Pharm. 2011, 415, 273–283. [Google Scholar] [CrossRef]
- Shilo, M.; Motiei, M.; Hana, P.; Popovtzer, R. Transport of nanoparticles through the blood-brain barrier for imaging and therapeutic applications. Nanoscale 2014, 6, 2146–2152. [Google Scholar] [CrossRef]
- Xin, H.; Sha, X.; Jiang, X.; Zhang, W.; Chen, L.; Fang, X. Anti-glioblastoma efficacy and safety of paclitaxel-loading Angiopep-conjugated dual targeting PEG-PCL nanoparticles. Biomaterials 2012, 33, 8167–8176. [Google Scholar] [CrossRef] [PubMed]
- Zhang, W.; Liu, Q.Y.; Haqqani, A.S.; Leclerc, S.; Liu, Z.; Fauteux, F.; Baumann, E.; Delaney, C.E.; Ly, D.; Star, A.T.; et al. Differential expression of receptors mediating receptor-mediated transcytosis (RMT) in brain microvessels, brain parenchyma and peripheral tissues of the mouse and the human. Fluids Barriers CNS 2020, 17, 47. [Google Scholar] [CrossRef] [PubMed]
- Hawkins, B.T.; Egleton, R.D.; Davis, T.P. Modulation of cerebral microvascular permeability by endothelial nicotinic acetylcholine receptors. Am. J. Physiol.-Heart Circ. Physiol. 2005, 289, H212–H219. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ramalho, M.J.; Sevin, E.; Gosselet, F.; Lima, J.; Coelho, M.A.N.; Loureiro, J.A.; Pereira, M.C. Receptor-mediated PLGA nanoparticles for glioblastoma multiforme treatment. Int. J. Pharm. 2018, 545, 84–92. [Google Scholar] [CrossRef]
- Kuang, Y.; Jiang, X.; Zhang, Y.; Lu, Y.; Ma, H.; Guo, Y.; Zhang, Y.; An, S.; Li, J.; Liu, L.; et al. Dual Functional Peptide-Driven Nanoparticles for Highly Efficient Glioma-Targeting and Drug Codelivery. Mol. Pharm. 2016, 13, 1599–1607. [Google Scholar] [CrossRef] [PubMed]
- Johnsen, K.B.; Bak, M.; Melander, F.; Thomsen, M.S.; Burkhart, A.; Kempen, P.J.; Andresen, T.L.; Moos, T. Modulating the antibody density changes the uptake and transport at the blood-brain barrier of both transferrin receptor-targeted gold nanoparticles and liposomal cargo. J. Control Release 2019, 295, 237–249. [Google Scholar] [CrossRef]
- Paris-Robidas, S.; Emond, V.; Tremblay, C.; Soulet, D.; Calon, F. In Vivo Labeling of Brain Capillary Endothelial Cells after Intravenous Injection of Monoclonal Antibodies Targeting the Transferrin Receptor. Mol. Pharmacol. 2011, 80, 32–39. [Google Scholar] [CrossRef] [Green Version]
- Mao, J.; Meng, X.; Zhao, C.; Yang, Y.; Liu, G. Development of transferrin-modified poly(lactic-co-glycolic acid) nanoparticles for glioma therapy. Anti-Cancer Drugs 2019, 30, 604–610. [Google Scholar] [CrossRef]
- Cabral Filho, P.E.; Cardoso, A.L.C.; Pereira, M.I.A.; Ramos, A.P.M.; Hallwass, F.; Castro, M.M.C.A.; Geraldes, C.F.G.C.; Santos, B.S.; Pedroso de Lima, M.C.; Pereira, G.A.L.; et al. CdTe quantum dots as fluorescent probes to study transferrin receptors in glioblastoma cells. Biochim. Biophys. Acta (BBA)—Gen. Subj. 2016, 1860, 28–35. [Google Scholar] [CrossRef] [Green Version]
- Roberts, R.L.; Fine, R.E.; Sandra, A. Receptor-mediated endocytosis of transferrin at the blood-brain barrier. J. Cell Sci. 1993, 104, 521–532. [Google Scholar] [CrossRef]
- Uchida, Y.; Ohtsuki, S.; Katsukura, Y.; Ikeda, C.; Suzuki, T.; Kamiie, J.; Terasaki, T. Quantitative targeted absolute proteomics of human blood-brain barrier transporters and receptors. J. Neurochem. 2011, 117, 333–345. [Google Scholar] [CrossRef] [PubMed]
- Maussang, D.; Rip, J.; van Kregten, J.; van den Heuvel, A.; van der Pol, S.; van der Boom, B.; Reijerkerk, A.; Chen, L.; de Boer, M.; Gaillard, P.; et al. Glutathione conjugation dose-dependently increases brain-specific liposomal drug delivery in vitro and in vivo. Drug Discov. Today Technol. 2016, 20, 59–69. [Google Scholar] [CrossRef] [PubMed]
- Da Silva-Candal, A.; Brown, T.; Krishnan, V.; Lopez-Loureiro, I.; Ávila-Gómez, P.; Pusuluri, A.; Pérez-Díaz, A.; Correa-Paz, C.; Hervella, P.; Castillo, J.; et al. Shape effect in active targeting of nanoparticles to inflamed cerebral endothelium under static and flow conditions. J. Control Release 2019, 309, 94–105. [Google Scholar] [CrossRef] [PubMed]
- Kolhar, P.; Anselmo, A.C.; Gupta, V.; Pant, K.; Prabhakarpandian, B.; Ruoslahti, E.; Mitragotri, S. Using shape effects to target antibody-coated nanoparticles to lung and brain endothelium. Proc. Natl. Acad. Sci. USA 2013, 110, 10753–10758. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Nowak, M.; Brown, T.D.; Graham, A.; Helgeson, M.E.; Mitragotri, S. Size, shape, and flexibility influence nanoparticle transport across brain endothelium under flow. Bioeng. Transl. Med. 2020, 5, e10153. [Google Scholar] [CrossRef] [Green Version]
- Takeshita, Y.; Ransohoff, R.M. Inflammatory cell trafficking across the blood-brain barrier: Chemokine regulation and in vitro models. Immunol. Rev. 2012, 248, 228–239. [Google Scholar] [CrossRef] [Green Version]
- Han, Y.; Li, X.; Zhang, Y.; Han, Y.; Chang, F.; Ding, J. Mesenchymal Stem Cells for Regenerative Medicine. Cells 2019, 8, 886. [Google Scholar] [CrossRef] [Green Version]
- Roger, M.; Clavreul, A.; Venier-Julienne, M.C.; Passirani, C.; Sindji, L.; Schiller, P.; Montero-Menei, C.; Menei, P. Mesenchymal stem cells as cellular vehicles for delivery of nanoparticles to brain tumors. Biomaterials 2010, 31, 8393–8401. [Google Scholar] [CrossRef]
- Li, L.; Guan, Y.; Liu, H.; Hao, N.; Liu, T.; Meng, X.; Fu, C.; Li, Y.; Qu, Q.; Zhang, Y.; et al. Silica Nanorattle–Doxorubicin-Anchored Mesenchymal Stem Cells for Tumor-Tropic Therapy. ACS Nano 2011, 5, 7462–7470. [Google Scholar] [CrossRef]
- Choi, M.-R.; Stanton-Maxey, K.J.; Stanley, J.K.; Levin, C.S.; Bardhan, R.; Akin, D.; Badve, S.; Sturgis, J.; Robinson, J.P.; Bashir, R.; et al. A Cellular Trojan Horse for Delivery of Therapeutic Nanoparticles into Tumors. Nano Lett. 2007, 7, 3759–3765. [Google Scholar] [CrossRef]
- Ibarra, L.E.; Beaugé, L.; Arias-Ramos, N.; Rivarola, V.A.; Chesta, C.A.; López-Larrubia, P.; Palacios, R.E. Trojan horse monocyte-mediated delivery of conjugated polymer nanoparticles for improved photodynamic therapy of glioblastoma. Nanomedicine 2020, 15, 1687–1707. [Google Scholar] [CrossRef] [PubMed]
- Li, Z.; Huang, H.; Tang, S.; Li, Y.; Yu, X.F.; Wang, H.; Li, P.; Sun, Z.; Zhang, H.; Liu, C.; et al. Small gold nanorods laden macrophages for enhanced tumor coverage in photothermal therapy. Biomaterials 2016, 74, 144–154. [Google Scholar] [CrossRef] [PubMed]
- Chu, D.; Gao, J.; Wang, Z. Neutrophil-Mediated Delivery of Therapeutic Nanoparticles across Blood Vessel Barrier for Treatment of Inflammation and Infection. ACS Nano 2015, 9, 11800–11811. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Steinfeld, U.; Pauli, C.; Kaltz, N.; Bergemann, C.; Lee, H.H. T lymphocytes as potential therapeutic drug carrier for cancer treatment. Int. J. Pharm. 2006, 311, 229–236. [Google Scholar] [CrossRef]
- Zhang, J.; Han, M.; Zhang, J.; Abdalla, M.; Sun, P.; Yang, Z.; Zhang, C.; Liu, Y.; Chen, C.; Jiang, X. Syphilis mimetic nanoparticles for cuproptosis-based synergistic cancer therapy via reprogramming copper metabolism. Int. J. Pharm. 2023, 640, 123025. [Google Scholar] [CrossRef]
- Ji, J.; Lian, W.; Zhang, Y.; Lin, D.; Wang, J.; Mo, Y.; Xu, X.; Hou, C.; Ma, C.; Zheng, Y.; et al. Preoperative administration of a biomimetic platelet nanodrug enhances postoperative drug delivery by bypassing thrombus. Int. J. Pharm. 2023, 636, 122851. [Google Scholar] [CrossRef]
- Zhuang, X.; Xiang, X.; Grizzle, W.; Sun, D.; Zhang, S.; Axtell, R.C.; Ju, S.; Mu, J.; Zhang, L.; Steinman, L.; et al. Treatment of Brain Inflammatory Diseases by Delivering Exosome Encapsulated Anti-inflammatory Drugs from the Nasal Region to the Brain. Mol. Ther. 2011, 19, 1769–1779. [Google Scholar] [CrossRef]
- Sousa, F.; Dhaliwal, H.K.; Gattacceca, F.; Sarmento, B.; Amiji, M.M. Enhanced anti-angiogenic effects of bevacizumab in glioblastoma treatment upon intranasal administration in polymeric nanoparticles. J. Control Release 2019, 309, 37–47. [Google Scholar] [CrossRef]
- Djupesland, P.G. Nasal drug delivery devices: Characteristics and performance in a clinical perspective—A review. Drug Deliv. Transl. Res. 2013, 3, 42–62. [Google Scholar] [CrossRef] [Green Version]
- Bobo, R.H.; Laske, D.W.; Akbasak, A.; Morrison, P.F.; Dedrick, R.L.; Oldfield, E.H. Convection-enhanced delivery of macromolecules in the brain. Proc. Natl. Acad. Sci. USA 1994, 91, 2076–2080. [Google Scholar] [CrossRef] [Green Version]
- Lonser, R.R.; Sarntinoranont, M.; Morrison, P.F.; Oldfield, E.H. Convection-enhanced delivery to the central nervous system. J. Neurosurg. 2015, 122, 697–706. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhou, Z.; Singh, R.; Souweidane, M.M. Convection-Enhanced Delivery for Diffuse Intrinsic Pontine Glioma Treatment. Curr. Neuropharmacol. 2017, 15, 116–128. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Souweidane, M.M.; Kramer, K.; Pandit-Taskar, N.; Zhou, Z.; Haque, S.; Zanzonico, P.; Carrasquillo, J.A.; Lyashchenko, S.K.; Thakur, S.B.; Donzelli, M.; et al. Convection-enhanced delivery for diffuse intrinsic pontine glioma: A single-centre, dose-escalation, phase 1 trial. Lancet Oncol. 2018, 19, 1040–1050. [Google Scholar] [CrossRef] [PubMed]
- Bander, E.D.; Ramos, A.D.; Wembacher-Schroeder, E.; Ivasyk, I.; Thomson, R.; Morgenstern, P.F.; Souweidane, M.M. Repeat convection-enhanced delivery for diffuse intrinsic pontine glioma. J. Neurosurg. Pediatr. 2020, 26, 661–666. [Google Scholar] [CrossRef] [PubMed]
- Mueller, S.; Kline, C.; Villanueva-Meyer, J.; Hoffman, C.; Raber, S.; Bonner, E.; Nazarian, J.; Lundy, S.; Molinaro, A.M.; Prados, M.; et al. EPCT-12. PNOC015: PHASE 1 STUDY OF MTX110 (AQUEOUS PANOBINOSTAT) DELIVERED BY CONVECTION ENHANCED DELIVERY (CED) IN CHILDREN WITH NEWLY DIAGNOSED DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG) PREVIOUSLY TREATED WITH RADIATION THERAPY. Neuro Oncol. 2020, 22, iii306. [Google Scholar] [CrossRef]
- Zacharoulis, S.; Szalontay, L.; CreveCoeur, T.; Neira, J.; Higgins, D.; Englander, Z.; Spinazzi, E.; Sethi, C.; Canoll, P.; Garvin, J. DDEL-07. A Phase I study examining the feasibility of intermittent convection-enhanced delivery (CED) of MTX110 for the treatment of children with newly diagnosed diffuse midline gliomas (DMGs). Neuro Oncol. 2022, 24, i35. [Google Scholar] [CrossRef]
- Heiss, J.D.; Jamshidi, A.; Shah, S.; Martin, S.; Wolters, P.L.; Argersinger, D.P.; Warren, K.E.; Lonser, R.R. Phase I trial of convection-enhanced delivery of IL13-Pseudomonas toxin in children with diffuse intrinsic pontine glioma. J. Neurosurg. Pediatr. 2018, 23, 333–342. [Google Scholar] [CrossRef] [Green Version]
- Kunwar, S.; Chang, S.; Westphal, M.; Vogelbaum, M.; Sampson, J.; Barnett, G.; Shaffrey, M.; Ram, Z.; Piepmeier, J.; Prados, M.; et al. Phase III randomized trial of CED of IL13-PE38QQR vs Gliadel wafers for recurrent glioblastoma. Neuro Oncol. 2010, 12, 871–881. [Google Scholar] [CrossRef] [Green Version]
- Sampson, J.H.; Archer, G.; Pedain, C.; Wembacher-Schröder, E.; Westphal, M.; Kunwar, S.; Vogelbaum, M.A.; Coan, A.; Herndon, J.E.; Raghavan, R.; et al. Poor drug distribution as a possible explanation for the results of the PRECISE trial. J. Neurosurg. 2010, 113, 301–309. [Google Scholar] [CrossRef]
- Mueller, S.; Polley, M.Y.; Lee, B.; Kunwar, S.; Pedain, C.; Wembacher-Schröder, E.; Mittermeyer, S.; Westphal, M.; Sampson, J.H.; Vogelbaum, M.A.; et al. Effect of imaging and catheter characteristics on clinical outcome for patients in the PRECISE study. J. Neurooncol. 2011, 101, 267–277. [Google Scholar] [CrossRef] [Green Version]
- Bredlau, A.L.; Dixit, S.; Chen, C.; Broome, A.M. Nanotechnology Applications for Diffuse Intrinsic Pontine Glioma. Curr. Neuropharmacol. 2017, 15, 104–115. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhang, R.; Saito, R.; Mano, Y.; Kanamori, M.; Sonoda, Y.; Kumabe, T.; Tominaga, T. Concentration rather than dose defines the local brain toxicity of agents that are effectively distributed by convection-enhanced delivery. J. Neurosci. Methods 2014, 222, 131–137. [Google Scholar] [CrossRef] [PubMed]
- Zacharoulis, S.; Columbia University. CED of MTX110 Newly Diagnosed Diffuse Midline Gliomas. Available online: https://ClinicalTrials.gov/show/NCT04264143 (accessed on 30 October 2021).
- Cheng, Z.; Zhang, J.; Liu, H.; Li, Y.; Zhao, Y.; Yang, E. Central Nervous System Penetration for Small Molecule Therapeutic Agents Does Not Increase in Multiple Sclerosis- and Alzheimer’s Disease-Related Animal Models Despite Reported Blood-Brain Barrier Disruption. Drug Metab. Dispos. 2010, 38, 1355–1361. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Somjen, G.; Segal, M.; Herreras, O. Osmotic-hypertensive opening of the blood-brain barrier in rats does not necessarily provide access for potassium to cerebral interstitial fluid. Exp. Physiol. 1991, 76, 507–514. [Google Scholar] [CrossRef] [Green Version]
- Nance, E.; Timbie, K.; Miller, G.W.; Song, J.; Louttit, C.; Klibanov, A.L.; Shih, T.-Y.; Swaminathan, G.; Tamargo, R.J.; Woodworth, G.F.; et al. Non-invasive delivery of stealth, brain-penetrating nanoparticles across the blood − brain barrier using MRI-guided focused ultrasound. J. Control Release 2014, 189, 123–132. [Google Scholar] [CrossRef] [Green Version]
- Nance, E.A.; Woodworth, G.F.; Sailor, K.A.; Shih, T.-Y.; Xu, Q.; Swaminathan, G.; Xiang, D.; Eberhart, C.; Hanes, J. A Dense Poly(Ethylene Glycol) Coating Improves Penetration of Large Polymeric Nanoparticles Within Brain Tissue. Sci. Transl. Med. 2012, 4, 149ra119. [Google Scholar] [CrossRef] [Green Version]
- Schneider, C.S.; Perez, J.G.; Cheng, E.; Zhang, C.; Mastorakos, P.; Hanes, J.; Winkles, J.A.; Woodworth, G.F.; Kim, A.J. Minimizing the non-specific binding of nanoparticles to the brain enables active targeting of Fn14-positive glioblastoma cells. Biomaterials 2015, 42, 42–51. [Google Scholar] [CrossRef] [Green Version]
- Matsumura, Y.; Maeda, H. A new concept for macromolecular therapeutics in cancer chemotherapy: Mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. Cancer Res. 1986, 46, 6387–6392. [Google Scholar]
- Gabizon, A.; Shmeeda, H.; Barenholz, Y. Pharmacokinetics of Pegylated Liposomal Doxorubicin. Clin. Pharmacokinet. 2003, 42, 419–436. [Google Scholar] [CrossRef]
- Mo, F.; Pellerino, A.; Soffietti, R.; Rudà, R. Blood–Brain Barrier in Brain Tumors: Biology and Clinical Relevance. Int. J. Mol. Sci. 2021, 22, 12654. [Google Scholar] [CrossRef]
- Siegal, T.; Horowitz, A.; Gabizon, A. Doxorubicin encapsulated in sterically stabilized liposomes for the treatment of a brain tumor model: Biodistribution and therapeutic efficacy. J. Neurosurg. 1995, 83, 1029–1037. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sarin, H.; Kanevsky, A.S.; Wu, H.; Brimacombe, K.R.; Fung, S.H.; Sousa, A.A.; Auh, S.; Wilson, C.M.; Sharma, K.; Aronova, M.A.; et al. Effective transvascular delivery of nanoparticles across the blood-brain tumor barrier into malignant glioma cells. J. Transl. Med. 2008, 6, 80. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Shein, S.A.; Kuznetsov, I.I.; Abakumova, T.O.; Chelushkin, P.S.; Melnikov, P.A.; Korchagina, A.A.; Bychkov, D.A.; Seregina, I.F.; Bolshov, M.A.; Kabanov, A.V.; et al. VEGF- and VEGFR2-Targeted Liposomes for Cisplatin Delivery to Glioma Cells. Mol. Pharm. 2016, 13, 3712–3723. [Google Scholar] [CrossRef] [PubMed]
- Shein, S.A.; Nukolova, N.V.; Korchagina, A.A.; Abakumova, T.O.; Kiuznetsov, I.I.; Abakumov, M.A.; Baklaushev, V.P.; Gurina, O.I.; Chekhonin, V.P. Site-Directed Delivery of VEGF-Targeted Liposomes into Intracranial C6 Glioma. Bull. Exp. Biol. Med. 2015, 158, 371–376. [Google Scholar] [CrossRef] [PubMed]
- Veiseh, M.; Gabikian, P.; Bahrami, S.B.; Veiseh, O.; Zhang, M.; Hackman, R.C.; Ravanpay, A.C.; Stroud, M.R.; Kusuma, Y.; Hansen, S.J.; et al. Tumor Paint: A Chlorotoxin:Cy5.5 Bioconjugate for Intraoperative Visualization of Cancer Foci. Cancer Res. 2007, 67, 6882–6888. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mortensen, J.H.; Jeppesen, M.; Pilgaard, L.; Agger, R.; Duroux, M.; Zachar, V.; Moos, T. Targeted Antiepidermal Growth Factor Receptor (Cetuximab) Immunoliposomes Enhance Cellular Uptake In Vitro and Exhibit Increased Accumulation in an Intracranial Model of Glioblastoma Multiforme. J. Drug Deliv. 2013, 2013, 209205. [Google Scholar] [CrossRef] [Green Version]
- Greenall, S.A.; McKenzie, M.; Seminova, E.; Dolezal, O.; Pearce, L.; Bentley, J.; Kuchibhotla, M.; Chen, S.C.; McDonald, K.L.; Kornblum, H.I.; et al. Most clinical anti-EGFR antibodies do not neutralize both wtEGFR and EGFRvIII activation in glioma. Neuro Oncol. 2019, 21, 1016–1027. [Google Scholar] [CrossRef]
- Pan, P.C.; Magge, R.S. Mechanisms of EGFR Resistance in Glioblastoma. Int. J. Mol. Sci. 2020, 21, 8471. [Google Scholar] [CrossRef]
- Dhar, D.; Ghosh, S.; Das, S.; Chatterjee, J. A review of recent advances in magnetic nanoparticle-based theranostics of glioblastoma. Nanomedicine 2022, 17, 107–132. [Google Scholar] [CrossRef]
- Ganipineni, L.P.; Ucakar, B.; Joudiou, N.; Bianco, J.; Danhier, P.; Zhao, M.; Bastiancich, C.; Gallez, B.; Danhier, F.; Préat, V. Magnetic targeting of paclitaxel-loaded poly(lactic-co-glycolic acid)-based nanoparticles for the treatment of glioblastoma. Int. J. Nanomed. 2018, 13, 4509–4521. [Google Scholar] [CrossRef] [Green Version]
- Heggannavar, G.B.; Hiremath, C.G.; Achari, D.D.; Pangarkar, V.G.; Kariduraganavar, M.Y. Development of Doxorubicin-Loaded Magnetic Silica–Pluronic F-127 Nanocarriers Conjugated with Transferrin for Treating Glioblastoma across the Blood–Brain Barrier Using an in Vitro Model. ACS Omega 2018, 3, 8017–8026. [Google Scholar] [CrossRef] [PubMed]
- Norouzi, M.; Yathindranath, V.; Thliveris, J.A.; Kopec, B.M.; Siahaan, T.J.; Miller, D.W. Doxorubicin-loaded iron oxide nanoparticles for glioblastoma therapy: A combinational approach for enhanced delivery of nanoparticles. Sci. Rep. 2020, 10, 11292. [Google Scholar] [CrossRef]
- Li, B.; Chen, X.; Qiu, W.; Zhao, R.; Duan, J.; Zhang, S.; Pan, Z.; Zhao, S.; Guo, Q.; Qi, Y.; et al. Synchronous Disintegration of Ferroptosis Defense Axis via Engineered Exosome-Conjugated Magnetic Nanoparticles for Glioblastoma Therapy. Adv. Sci. 2022, 9, 2105451. [Google Scholar] [CrossRef] [PubMed]
- Calatayud, M.P.; Soler, E.; Torres, T.E.; Campos-Gonzalez, E.; Junquera, C.; Ibarra, M.R.; Goya, G.F. Cell damage produced by magnetic fluid hyperthermia on microglial BV2 cells. Sci. Rep. 2017, 7, 8627. [Google Scholar] [CrossRef] [Green Version]
- Shen, Z.; Liu, T.; Yang, Z.; Zhou, Z.; Tang, W.; Fan, W.; Liu, Y.; Mu, J.; Li, L.; Bregadze, V.I.; et al. Small-sized gadolinium oxide based nanoparticles for high-efficiency theranostics of orthotopic glioblastoma. Biomaterials 2020, 235, 119783. [Google Scholar] [CrossRef] [PubMed]
- Kefayat, A.; Ghahremani, F.; Motaghi, H.; Amouheidari, A. Ultra-small but ultra-effective: Folic acid-targeted gold nanoclusters for enhancement of intracranial glioma tumors' radiation therapy efficacy. Nanomed. Nanotechnol. Biol. Med. 2019, 16, 173–184. [Google Scholar] [CrossRef]
- Goubault, C.; Jarry, U.; Bostoen, M.; Eliat, P.A.; Kahn, M.L.; Pedeux, R.; Guillaudeux, T.; Gauffre, F.; Chevance, S. Radiosensitizing Fe-Au nanocapsules (hybridosomes(R)) increase survival of GL261 brain tumor-bearing mice treated by radiotherapy. Nanomedicine 2022, 40, 102499. [Google Scholar] [CrossRef]
- Jing, Z.; Li, M.; Wang, H.; Yang, Z.; Zhou, S.; Ma, J.; Meng, E.; Zhang, H.; Liang, W.; Hu, W.; et al. Gallic acid-gold nanoparticles enhance radiation-induced cell death of human glioma U251 cells. IUBMB Life 2021, 73, 398–407. [Google Scholar] [CrossRef]
- Hsieh, H.T.; Huang, H.C.; Chung, C.W.; Chiang, C.C.; Hsia, T.; Wu, H.F.; Huang, R.L.; Chiang, C.S.; Wang, J.; Lu, T.T.; et al. CXCR4-targeted nitric oxide nanoparticles deliver PD-L1 siRNA for immunotherapy against glioblastoma. J. Control Release 2022, 352, 920–930. [Google Scholar] [CrossRef]
- Zhang, Y.; Ren, Y.; Xu, H.; Li, L.; Qian, F.; Wang, L.; Quan, A.; Ma, H.; Liu, H.; Yu, R. Cascade-Responsive 2-DG Nanocapsules Encapsulate aV-siCPT1C Conjugates to Inhibit Glioblastoma through Multiple Inhibition of Energy Metabolism. ACS Appl. Mater. Interfaces 2023, 15, 10356–10370. [Google Scholar] [CrossRef]
- Rinaldi, A.; Caraffi, R.; Grazioli, M.V.; Oddone, N.; Giardino, L.; Tosi, G.; Vandelli, M.A.; Calzà, L.; Ruozi, B.; Duskey, J.T. Applications of the ROS-Responsive Thioketal Linker for the Production of Smart Nanomedicines. Polymers 2022, 14, 687. [Google Scholar] [CrossRef] [PubMed]
- Oddone, N.; Boury, F.; Garcion, E.; Grabrucker, A.M.; Martinez, M.C.; Da Ros, F.; Janaszewska, A.; Forni, F.; Vandelli, M.A.; Tosi, G.; et al. Synthesis, Characterization, and In Vitro Studies of an Reactive Oxygen Species (ROS)-Responsive Methoxy Polyethylene Glycol-Thioketal-Melphalan Prodrug for Glioblastoma Treatment. Front. Pharmacol. 2020, 11, 574. [Google Scholar] [CrossRef] [PubMed]
- Liu, Z.; Zhou, Z.; Dang, Q.; Xu, H.; Lv, J.; Li, H.; Han, X. Immunosuppression in tumor immune microenvironment and its optimization from CAR-T cell therapy. Theranostics 2022, 12, 6273–6290. [Google Scholar] [CrossRef]
- Balakrishnan, P.B.; Sweeney, E.E. Nanoparticles for Enhanced Adoptive T Cell Therapies and Future Perspectives for CNS Tumors. Front. Immunol. 2021, 12, 600659. [Google Scholar] [CrossRef]
- Chang, Y.; Cai, X.; Syahirah, R.; Yao, Y.; Xu, Y.; Jin, G.; Bhute, V.J.; Torregrosa-Allen, S.; Elzey, B.D.; Won, Y.-Y.; et al. CAR-neutrophil mediated delivery of tumor-microenvironment responsive nanodrugs for glioblastoma chemo-immunotherapy. Nat. Commun. 2023, 14, 2266. [Google Scholar] [CrossRef] [PubMed]
- Zhang, F.; Stephan, S.B.; Ene, C.I.; Smith, T.T.; Holland, E.C.; Stephan, M.T. Nanoparticles That Reshape the Tumor Milieu Create a Therapeutic Window for Effective T-cell Therapy in Solid Malignancies. Cancer Res. 2018, 78, 3718–3730. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chen, Q.; Hu, Q.; Dukhovlinova, E.; Chen, G.; Ahn, S.; Wang, C.; Ogunnaike, E.A.; Ligler, F.S.; Dotti, G.; Gu, Z. Photothermal Therapy Promotes Tumor Infiltration and Antitumor Activity of CAR T Cells. Adv. Mater. 2019, 31, 1900192. [Google Scholar] [CrossRef] [PubMed]
Nanoparticle Class | Strengths | Weaknesses | References |
---|---|---|---|
Lipid-based NP | Simplicity of manufacturing process | Rapid elimination from bloodstream | [58,59,60,61,62,63,64] |
Payload flexibility | CARPA | ||
Potential for surface modification | |||
Biocompatibility | |||
Polymeric NP | Precise control over physicochemical properties and drug release profile | Rapid elimination from bloodstream | [65,66,67,68,69,70,71] |
Payload flexibility | Relatively low drug loading capacity | ||
Potential for surface modification | |||
Inorganic NP | Variability in sizes, shapes, and constructs | Low solubility, aggregation | [72,73,74,75,76] |
Unique magnetic and/or photothermal properties, allowing theragnostic applications | Toxicity concerns | ||
Biological NP | Biocompatibility | Rapid elimination from bloodstream | [61,77,78,79,80,81] |
Inherently functionalized membrane | Low production scalability | ||
Payload flexibility | More complex drug loading process | ||
Low drug loading capacity |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Vanbilloen, W.J.F.; Rechberger, J.S.; Anderson, J.B.; Nonnenbroich, L.F.; Zhang, L.; Daniels, D.J. Nanoparticle Strategies to Improve the Delivery of Anticancer Drugs across the Blood–Brain Barrier to Treat Brain Tumors. Pharmaceutics 2023, 15, 1804. https://doi.org/10.3390/pharmaceutics15071804
Vanbilloen WJF, Rechberger JS, Anderson JB, Nonnenbroich LF, Zhang L, Daniels DJ. Nanoparticle Strategies to Improve the Delivery of Anticancer Drugs across the Blood–Brain Barrier to Treat Brain Tumors. Pharmaceutics. 2023; 15(7):1804. https://doi.org/10.3390/pharmaceutics15071804
Chicago/Turabian StyleVanbilloen, Wouter J. F., Julian S. Rechberger, Jacob B. Anderson, Leo F. Nonnenbroich, Liang Zhang, and David J. Daniels. 2023. "Nanoparticle Strategies to Improve the Delivery of Anticancer Drugs across the Blood–Brain Barrier to Treat Brain Tumors" Pharmaceutics 15, no. 7: 1804. https://doi.org/10.3390/pharmaceutics15071804
APA StyleVanbilloen, W. J. F., Rechberger, J. S., Anderson, J. B., Nonnenbroich, L. F., Zhang, L., & Daniels, D. J. (2023). Nanoparticle Strategies to Improve the Delivery of Anticancer Drugs across the Blood–Brain Barrier to Treat Brain Tumors. Pharmaceutics, 15(7), 1804. https://doi.org/10.3390/pharmaceutics15071804