Controlled Release of Therapeutics from Thermoresponsive Nanogels: A Thermal Magnetic Resonance Feasibility Study
Abstract
1. Introduction
2. Results
2.1. Temperature Simulations of the Phantom
2.2. RF Heating of the Experimental Phantom
2.3. Thermoresponsive Nanogel Synthesis and Characterization
2.4. Nanogel Release Profile using a Water Bath for Temperature Modulation
2.5. Nanogel Release Profile using ThermalMR for Temperature Modulation
3. Discussion
4. Materials and Methods
4.1. Phantom Design for RF-Induced Heating in MRI Scanner
4.2. Experimental Setup for RF-Induced Heating in an MRI Scanner
4.3. Synthesis and Characterization of Thermoresponsive Nanogels
4.4. Protein Encapsulation in the Thermoresponsive Nanogels
4.5. Evaluation of BSA Release using a Water Bath
4.6. RF-Induced Heating Paradigm and Release Study
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
- Besse, H.C.; Barten-van Rijbroek, A.D.; van der Wurff-Jacobs, K.M.G.; Bos, C.; Moonen, C.T.W.; Deckers, R. Tumor drug distribution after local drug delivery by hyperthermia, in vivo. Cancers 2019, 11, 1512. [Google Scholar] [CrossRef] [PubMed]
- Barreto, J.A.; O’Malley, W.; Kubeil, M.; Graham, B.; Stephan, H.; Spiccia, L. Nanomaterials: Applications in cancer imaging and therapy. Adv. Mater. 2011, 23, H18–H40. [Google Scholar] [CrossRef] [PubMed]
- Zhao, C.-Y.; Cheng, R.; Yang, Z.; Tian, Z.-M. Nanotechnology for cancer therapy based on chemotherapy. Molecules 2018, 23, 826. [Google Scholar] [CrossRef] [PubMed]
- Hirakura, T.; Yasugi, K.; Nemoto, T.; Sato, M.; Shimoboji, T.; Aso, Y.; Morimoto, N.; Akiyoshi, K. Hybrid hyaluronan hydrogel encapsulating nanogel as a protein nanocarrier: New system for sustained delivery of protein with a chaperone-like function. J. Control. Release 2010, 142, 483–489. [Google Scholar] [CrossRef] [PubMed]
- Panyam, J.; Labhasetwar, V. Biodegradable nanoparticles for drug and gene delivery to cells and tissue. Adv. Drug Deliv. Rev. 2003, 55, 329–347. [Google Scholar] [CrossRef]
- Lynn, D.M.; Amiji, M.M.; Langer, R. pH-responsive polymer microspheres: Rapid release of encapsulated material within the range of intracellular pH. Angew. Chemie Int. Ed. 2001, 40, 1707–1710. [Google Scholar] [CrossRef]
- Wu, X.; Wang, Z.; Zhu, D.; Zong, S.; Yang, L.; Zhong, Y.; Cui, Y. pH and thermo dual-stimuli-responsive drug carrier based on mesoporous silica nanoparticles encapsulated in a copolymer–lipid bilayer. ACS Appl. Mater. Interfaces 2013, 5, 10895–10903. [Google Scholar] [CrossRef]
- Molina, M.; Giulbudagian, M.; Calderón, M. Positively charged thermoresponsive nanogels for anticancer drug delivery. Macromol. Chem. Phys. 2014, 215, 2414–2419. [Google Scholar] [CrossRef]
- Rwei, A.Y.; Wang, W.; Kohane, D.S. Photoresponsive nanoparticles for drug delivery. Nano Today 2015, 10, 451–467. [Google Scholar] [CrossRef]
- Dunn, A.E.; Dunn, D.J.; Macmillan, A.; Whan, R.; Stait-Gardner, T.; Price, W.S.; Lim, M.; Boyer, C. Spatial and temporal control of drug release through pH and alternating magnetic field induced breakage of Schiff base bonds. Polym. Chem. 2014, 5, 3311–3315. [Google Scholar] [CrossRef]
- Seynhaeve, A.L.B.; Amin, M.; Haemmerich, D.; van Rhoon, G.C.; Ten Hagen, T.L.M. Hyperthermia and smart drug delivery systems for solid tumor therapy. Adv. Drug Deliv. Rev. 2020. [Google Scholar] [CrossRef] [PubMed]
- Wolinsky, J.B.; Colson, Y.L.; Grinstaff, M.W. Local drug delivery strategies for cancer treatment: Gels, nanoparticles, polymeric films, rods, and wafers. J. Control. release 2012, 159, 14–26. [Google Scholar] [CrossRef] [PubMed]
- Theune, L.E.; Charbaji, R.; Kar, M.; Wedepohl, S.; Hedtrich, S.; Calderón, M. Critical parameters for the controlled synthesis of nanogels suitable for temperature-triggered protein delivery. Mater. Sci. Eng. C 2019, 100, 141–151. [Google Scholar] [CrossRef] [PubMed]
- Ramos, J.; Imaz, A.; Forcada, J. Temperature-sensitive nanogels: Poly (N-vinylcaprolactam) versus poly (N-isopropylacrylamide). Polym. Chem. 2012, 3, 852–856. [Google Scholar] [CrossRef]
- Lin, J.C. Electromagnetic Fields in Biological Systems; CRC Press: Boca Raton, FL, USA, 2011; ISBN 143985999X. [Google Scholar]
- Kok, H.P.; Crezee, J. A comparison of the heating characteristics of capacitive and radiative superficial hyperthermia. Int. J. Hyperth. 2017, 33, 378–386. [Google Scholar] [CrossRef] [PubMed]
- Lin, C.-H.; Aljuffali, I.A.; Fang, J.-Y. Lasers as an approach for promoting drug delivery via skin. Expert Opin. Drug Deliv. 2014, 11, 599–614. [Google Scholar] [CrossRef]
- Ahmed, M.; Liu, Z.; Lukyanov, A.N.; Signoretti, S.; Horkan, C.; Monsky, W.L.; Torchilin, V.P.; Goldberg, S.N. Combination radiofrequency ablation with intratumoral liposomal doxorubicin: Effect on drug accumulation and coagulation in multiple tissues and tumor types in animals. Radiology 2005, 235, 469–477. [Google Scholar] [CrossRef]
- Aubry, J.-F.; Pauly, K.B.; Moonen, C.; Haar, G.; Ries, M.; Salomir, R.; Sokka, S.; Sekins, K.M.; Shapira, Y.; Ye, F. The road to clinical use of high-intensity focused ultrasound for liver cancer: Technical and clinical consensus. J. Ther. Ultrasound 2013, 1, 13. [Google Scholar] [CrossRef]
- Cranston, D. A review of high intensity focused ultrasound in relation to the treatment of renal tumours and other malignancies. Ultrason. Sonochem. 2015, 27, 654–658. [Google Scholar] [CrossRef]
- Grüll, H.; Langereis, S. Hyperthermia-triggered drug delivery from temperature-sensitive liposomes using MRI-guided high intensity focused ultrasound. J. Control. Release 2012, 161, 317–327. [Google Scholar] [CrossRef]
- May, J.P.; Li, S.-D. Hyperthermia-induced drug targeting. Expert Opin. Drug Deliv. 2013, 10, 511–527. [Google Scholar] [CrossRef]
- Ojha, T.; Pathak, V.; Shi, Y.; Hennink, W.E.; Moonen, C.T.W.; Storm, G.; Kiessling, F.; Lammers, T. Pharmacological and physical vessel modulation strategies to improve EPR-mediated drug targeting to tumors. Adv. Drug Deliv. Rev. 2017, 119, 44–60. [Google Scholar] [CrossRef] [PubMed]
- Hijnen, N.; Kneepkens, E.; de Smet, M.; Langereis, S.; Heijman, E.; Grüll, H. Thermal combination therapies for local drug delivery by magnetic resonance-guided high-intensity focused ultrasound. Proc. Natl. Acad. Sci. USA 2017, 114, E4802–E4811. [Google Scholar] [CrossRef] [PubMed]
- Bing, C.; Patel, P.; Staruch, R.M.; Shaikh, S.; Nofiele, J.; Wodzak Staruch, M.; Szczepanski, D.; Williams, N.S.; Laetsch, T.; Chopra, R. Longer heating duration increases localized doxorubicin deposition and therapeutic index in Vx2 tumors using MR-HIFU mild hyperthermia and thermosensitive liposomal doxorubicin. Int. J. Hyperth. 2019, 36, 196–203. [Google Scholar] [CrossRef] [PubMed]
- Staruch, R.M.; Hynynen, K.; Chopra, R. Hyperthermia-mediated doxorubicin release from thermosensitive liposomes using MR-HIFU: Therapeutic effect in rabbit Vx2 tumours. Int. J. Hyperth. 2015, 31, 118–133. [Google Scholar] [CrossRef]
- Paulides, M.M.; Trefna, H.D.; Curto, S.; Rodrigues, D.B. Recent technological advancements in radiofrequency-and microwave-mediated hyperthermia for enhancing drug delivery. Adv. Drug Deliv. Rev. 2020. [Google Scholar] [CrossRef] [PubMed]
- Hildebrandt, B.; Gellermann, J.; Riess, H.; Wust, P. Induced hyperthermia in the reatment of cancer. In Cancer Management in Man: Chemotherapy, Biological Therapy, Hyperthermia and supporting Measures; Springer: Dordrecht, The Netherlands, 2011; Volume 13, pp. 365–377. [Google Scholar]
- Winter, L.; Oezerdem, C.; Hoffmann, W.; van de Lindt, T.; Periquito, J.; Ji, Y.; Ghadjar, P.; Budach, V.; Wust, P.; Niendorf, T. Thermal magnetic resonance: Physics considerations and electromagnetic field simulations up to 23.5 Tesla (1GHz). Radiat. Oncol. 2015, 10, 201. [Google Scholar] [CrossRef]
- Winter, L.; Özerdem, C.; Hoffmann, W.; Santoro, D.; Müller, A.; Waiczies, H.; Seemann, R.; Graessl, A.; Wust, P.; Niendorf, T. Design and evaluation of a hybrid radiofrequency applicator for magnetic resonance imaging and RF induced hyperthermia: Electromagnetic field simulations up to 14.0 Tesla and proof-of-concept at 7.0 Tesla. PLoS ONE 2013, 8, e61661. [Google Scholar] [CrossRef]
- Oberacker, E.; Kuehne, A.; Nadobny, J.; Zschaeck, S.; Weihrauch, M.; Waiczies, H.; Ghadjar, P.; Wust, P.; Niendorf, T.; Winter, L. Radiofrequency applicator concepts for simultaneous MR imaging and hyperthermia treatment of glioblastoma multiforme. Curr. Dir. Biomed. Eng. 2017, 3, 473–477. [Google Scholar] [CrossRef]
- Kuehne, A.; Oberacker, E.; Waiczies, H.; Niendorf, T. Solving the Time-and Frequency-Multiplexed Problem of Constrained Radiofrequency Induced Hyperthermia. Cancers 2020, 12, 1072. [Google Scholar] [CrossRef]
- Eigentler, T.W.; Winter, L.; Han, H.; Oberacker, E.; Kuehne, A.; Waiczies, H.; Schmitter, S.; Boehmert, L.; Prinz, C.; Trefna, H.D. Wideband Self-Grounded Bow-Tie Antenna for Thermal MR. NMR Biomed. 2020, 33, e4274. [Google Scholar] [CrossRef] [PubMed]
- Miceli, E.; Kuropka, B.; Rosenauer, C.; Osorio Blanco, E.R.; Theune, L.E.; Kar, M.; Weise, C.; Morsbach, S.; Freund, C.; Calderón, M. Understanding the elusive protein corona of thermoresponsive nanogels. Nanomedicine 2018, 13, 2657–2668. [Google Scholar] [CrossRef] [PubMed]
- Plank, R.; Yealland, G.; Miceli, E.; Cunha, D.L.; Graff, P.; Thomforde, S.; Gruber, R.; Moosbrugger-Martinz, V.; Eckl, K.; Calderón, M. Transglutaminase 1 Replacement Therapy Successfully Mitigates the Autosomal Recessive Congenital Ichthyosis Phenotype in Full-Thickness Skin Disease Equivalents. J. Investig. Dermatol. 2019, 139, 1191–1195. [Google Scholar] [CrossRef] [PubMed]
- Giulbudagian, M.; Yealland, G.; Hönzke, S.; Edlich, A.; Geisendörfer, B.; Kleuser, B.; Hedtrich, S.; Calderón, M. Breaking the barrier-potent anti-inflammatory activity following efficient topical delivery of etanercept using thermoresponsive nanogels. Theranostics 2018, 8, 450. [Google Scholar] [CrossRef] [PubMed]
- De León, A.S.; Molina, M.; Wedepohl, S.; Muñoz-Bonilla, A.; Rodríguez-Hernández, J.; Calderón, M. Immobilization of stimuli-responsive nanogels onto honeycomb porous surfaces and controlled release of proteins. Langmuir 2016, 32, 1854–1862. [Google Scholar] [CrossRef] [PubMed]
- Witting, M.; Molina, M.; Obst, K.; Plank, R.; Eckl, K.M.; Hennies, H.C.; Calderón, M.; Frieß, W.; Hedtrich, S. Thermosensitive dendritic polyglycerol-based nanogels for cutaneous delivery of biomacromolecules. Nanomed. Nanotechnol. Biol. Med. 2015, 11, 1179–1187. [Google Scholar] [CrossRef]
- Landon, C.D.; Park, J.-Y.; Needham, D.; Dewhirst, M.W. Nanoscale drug delivery and hyperthermia: The materials design and preclinical and clinical testing of low temperature-sensitive liposomes used in combination with mild hyperthermia in the treatment of local cancer. Open Nanomed. J. 2011, 3, 38. [Google Scholar] [CrossRef]
- De Smet, M.; Langereis, S.; van den Bosch, S.; Grüll, H. Temperature-sensitive liposomes for doxorubicin delivery under MRI guidance. J. Control. Release 2010, 143, 120–127. [Google Scholar] [CrossRef]
- Niendorf, T.; Sodickson, D.K. Parallel imaging in cardiovascular MRI: Methods and applications. NMR Biomed. Int. J. Devoted Dev. Appl. Magn. Reson. Vivo 2006, 19, 325–341. [Google Scholar] [CrossRef]
- Sodickson, D.K.; Hardy, C.J.; Zhu, Y.; Giaquinto, R.O.; Gross, P.; Kenwood, G.; Niendorf, T.; Lejay, H.; McKenzie, C.A.; Ohliger, M.A. Rapid Volumetric MRI Using Parallel Imaging With Order-of-Magnitude Accelerations and a 32-Element RF Coil Array: Feasibility and implications1. Acad. Radiol. 2005, 12, 626–635. [Google Scholar] [CrossRef][Green Version]
- Fuchs, K.; Hezel, F.; Klix, S.; Mekle, R.; Wuerfel, J.; Niendorf, T. Simultaneous dual contrast weighting using double echo rapid acquisition with relaxation enhancement (RARE) imaging. Magn. Reson. Med. 2014, 72, 1590–1598. [Google Scholar] [CrossRef] [PubMed]
- Paul, K.; Huelnhagen, T.; Oberacker, E.; Wenz, D.; Kuehne, A.; Waiczies, H.; Schmitter, S.; Stachs, O.; Niendorf, T. Multiband diffusion-weighted MRI of the eye and orbit free of geometric distortions using a RARE-EPI hybrid. NMR Biomed. 2018, 31, e3872. [Google Scholar] [CrossRef] [PubMed]
- Ji, Y.; Waiczies, H.; Winter, L.; Neumanova, P.; Hofmann, D.; Rieger, J.; Mekle, R.; Waiczies, S.; Niendorf, T. Eight-channel transceiver RF coil array tailored for 1H/19F MR of the human knee and fluorinated drugs at 7.0 T. NMR Biomed. 2015, 28, 726–737. [Google Scholar] [CrossRef]
- Prinz, C.; Delgado, P.R.; Eigentler, T.W.; Starke, L.; Niendorf, T.; Waiczies, S. Toward 19 F magnetic resonance thermometry: Spin–lattice and spin–spin-relaxation times and temperature dependence of fluorinated drugs at 9.4 T. Magn. Reson. Mater. Phys. Biol. Med. 2019, 32, 51–61. [Google Scholar] [CrossRef] [PubMed]
- Gerecke, C.; Edlich, A.; Giulbudagian, M.; Schumacher, F.; Zhang, N.; Said, A.; Yealland, G.; Lohan, S.B.; Neumann, F.; Meinke, M.C. Biocompatibility and characterization of polyglycerol-based thermoresponsive nanogels designed as novel drug-delivery systems and their intracellular localization in keratinocytes. Nanotoxicology 2017, 11, 267–277. [Google Scholar] [CrossRef] [PubMed]
- Navarro, L.; Theune, L.E.; Calderón, M. Effect of crosslinking density on thermoresponsive nanogels: A study on the size control and the kinetics release of biomacromolecules. Eur. Polym. J. 2020, 124, 109478. [Google Scholar] [CrossRef]
- Hervault, A.; Dunn, A.E.; Lim, M.; Boyer, C.; Mott, D.; Maenosono, S.; Thanh, N.T.K. Doxorubicin loaded dual pH-and thermo-responsive magnetic nanocarrier for combined magnetic hyperthermia and targeted controlled drug delivery applications. Nanoscale 2016, 8, 12152–12161. [Google Scholar] [CrossRef] [PubMed]
- Peller, M.; Willerding, L.; Limmer, S.; Hossann, M.; Dietrich, O.; Ingrisch, M.; Sroka, R.; Lindner, L.H. Surrogate MRI markers for hyperthermia-induced release of doxorubicin from thermosensitive liposomes in tumors. J. Control. Release 2016, 237, 138–146. [Google Scholar] [CrossRef]
- Edlich, A.; Gerecke, C.; Giulbudagian, M.; Neumann, F.; Hedtrich, S.; Schäfer-Korting, M.; Ma, N.; Calderon, M.; Kleuser, B. Specific uptake mechanisms of well-tolerated thermoresponsive polyglycerol-based nanogels in antigen-presenting cells of the skin. Eur. J. Pharm. Biopharm. 2017, 116, 155–163. [Google Scholar] [CrossRef]
- Issels, R.D.; Lindner, L.H.; Verweij, J.; Wust, P.; Reichardt, P.; Schem, B.-C.; Abdel-Rahman, S.; Daugaard, S.; Salat, C.; Wendtner, C.-M. Neo-adjuvant chemotherapy alone or with regional hyperthermia for localised high-risk soft-tissue sarcoma: A randomised phase 3 multicentre study. Lancet Oncol. 2010, 11, 561–570. [Google Scholar] [CrossRef]
- Issels, R.D. Hyperthermia adds to chemotherapy. Eur. J. Cancer 2008, 44, 2546–2554. [Google Scholar] [CrossRef] [PubMed]
- Liu, D.; Yang, F.; Xiong, F.; Gu, N. The smart drug delivery system and its clinical potential. Theranostics 2016, 6, 1306. [Google Scholar] [CrossRef] [PubMed]
- Rimondino, G.N.; Miceli, E.; Molina, M.; Wedepohl, S.; Thierbach, S.; Rühl, E.; Strumia, M.; Martinelli, M.; Calderón, M. Rational design of dendritic thermoresponsive nanogels that undergo phase transition under endolysosomal conditions. J. Mater. Chem. B 2017, 5, 866–874. [Google Scholar] [CrossRef] [PubMed]
- Willerding, L.; Limmer, S.; Hossann, M.; Zengerle, A.; Wachholz, K.; ten Hagen, T.L.M.; Koning, G.A.; Sroka, R.; Lindner, L.H.; Peller, M. Method of hyperthermia and tumor size influence effectiveness of doxorubicin release from thermosensitive liposomes in experimental tumors. J. Control. Release 2016, 222, 47–55. [Google Scholar] [CrossRef]
- Trattnig, S.; Springer, E.; Bogner, W.; Hangel, G.; Strasser, B.; Dymerska, B.; Cardoso, P.L.; Robinson, S.D. Key clinical benefits of neuroimaging at 7 T. Neuroimage 2018, 168, 477–489. [Google Scholar] [CrossRef]
- Obusez, E.C.; Lowe, M.; Oh, S.-H.; Wang, I.; Bullen, J.; Ruggieri, P.; Hill, V.; Lockwood, D.; Emch, T.; Moon, D. 7T MR of intracranial pathology: Preliminary observations and comparisons to 3T and 1.5 T. Neuroimage 2018, 168, 459–476. [Google Scholar] [CrossRef]
- De Cocker, L.J.L.; Lindenholz, A.; Zwanenburg, J.J.M.; van der Kolk, A.G.; Zwartbol, M.; Luijten, P.R.; Hendrikse, J. Clinical vascular imaging in the brain at 7 T. Neuroimage 2018, 168, 452–458. [Google Scholar] [CrossRef] [PubMed]
- Niendorf, T.; Schulz-Menger, J.; Paul, K.; Huelnhagen, T.; Ferrari, V.A.; Hodge, R. High field cardiac magnetic resonance imaging: A case for ultrahigh field cardiac magnetic resonance. Circ. Cardiovasc. Imaging 2017, 10, e005460. [Google Scholar] [CrossRef]
- Klix, S.; Els, A.; Paul, K.; Graessl, A.; Oezerdem, C.; Weinberger, O.; Winter, L.; Thalhammer, C.; Huelnhagen, T.; Rieger, J. On the subjective acceptance during cardiovascular magnetic resonance imaging at 7.0 Tesla. J. Cardiovasc. Magn. Reson. 2015, 17, P13. [Google Scholar] [CrossRef]
- Versluis, M.J.; Teeuwisse, W.M.; Kan, H.E.; van Buchem, M.A.; Webb, A.G.; van Osch, M.J. Subject tolerance of 7 T MRI examinations. J. Magn. Reson. Imaging 2013, 38, 722–725. [Google Scholar] [CrossRef]
- Rauschenberg, J.; Nagel, A.M.; Ladd, S.C.; Theysohn, J.M.; Ladd, M.E.; Möller, H.E.; Trampel, R.; Turner, R.; Pohmann, R.; Scheffler, K. Multicenter study of subjective acceptance during magnetic resonance imaging at 7 and 9.4 T. Invest. Radiol. 2014, 49, 249–259. [Google Scholar] [CrossRef]
- Winter, L.; Niendorf, T. Electrodynamics and radiofrequency antenna concepts for human magnetic resonance at 23.5 T (1 GHz) and beyond. Magn. Reson. Mater. Physics, Biol. Med. 2016, 29, 641–656. [Google Scholar] [CrossRef] [PubMed]
- Ji, Y.; Hoffmann, W.; Pham, M.; Dunn, A.E.; Han, H.; Özerdem, C.; Waiczies, H.; Rohloff, M.; Endemann, B.; Boyer, C.; et al. High peak and high average radiofrequency power transmit/receive switch for thermal magnetic resonance. Magn. Reson. Med. 2018, 80, 2246–2255. [Google Scholar] [CrossRef] [PubMed]
- Cuggino, J.C.; Strumia, M.C.; Welker, P.; Licha, K.; Steinhilber, D.; Mutihac, R.-C.; Calderón, M. Thermosensitive nanogels based on dendritic polyglycerol and N-isopropylacrylamide for biomedical applications. Soft Matter 2011, 7, 11259–11266. [Google Scholar] [CrossRef]
- Ishihara, Y.; Calderon, A.; Watanabe, H.; Okamoto, K.; Suzuki, Y.; Kuroda, K.; Suzuki, Y. A precise and fast temperature mapping using water proton chemical shift. Magn. Reson. Med. 1995, 34, 814–823. [Google Scholar] [CrossRef]
- Rieke, V.; Butts Pauly, K. MR thermometry. J. Magn. Reson. Imaging Off. J. Int. Soc. Magn. Reson. Med. 2008, 27, 376–390. [Google Scholar] [CrossRef] [PubMed]
- Wonneberger, U.; Schnackenburg, B.; Wlodarczyk, W.; Walter, T.; Streitparth, F.; Rump, J.; Teichgräber, U.K.M. Intradiscal temperature monitoring using double gradient-echo pulse sequences at 1.0 T. J. Magn. Reson. Imaging 2010, 31, 1499–1503. [Google Scholar] [CrossRef]
- Fuchs, V.R.; Sox Jr, H.C. Physicians’ views of the relative importance of thirty medical innovations. Health Aff. 2001, 20, 30–42. [Google Scholar] [CrossRef]
- Vyas, K. 10 Medical Inventions of All Time That Changed the World. Available online: https://interestingengineering.com/10-medical-inventions-of-all-time-that-changed-the-world (accessed on 29 August 2019).
© 2020 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 (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Ji, Y.; Winter, L.; Navarro, L.; Ku, M.-C.; Periquito, J.S.; Pham, M.; Hoffmann, W.; Theune, L.E.; Calderón, M.; Niendorf, T. Controlled Release of Therapeutics from Thermoresponsive Nanogels: A Thermal Magnetic Resonance Feasibility Study. Cancers 2020, 12, 1380. https://doi.org/10.3390/cancers12061380
Ji Y, Winter L, Navarro L, Ku M-C, Periquito JS, Pham M, Hoffmann W, Theune LE, Calderón M, Niendorf T. Controlled Release of Therapeutics from Thermoresponsive Nanogels: A Thermal Magnetic Resonance Feasibility Study. Cancers. 2020; 12(6):1380. https://doi.org/10.3390/cancers12061380
Chicago/Turabian StyleJi, Yiyi, Lukas Winter, Lucila Navarro, Min-Chi Ku, João S. Periquito, Michal Pham, Werner Hoffmann, Loryn E. Theune, Marcelo Calderón, and Thoralf Niendorf. 2020. "Controlled Release of Therapeutics from Thermoresponsive Nanogels: A Thermal Magnetic Resonance Feasibility Study" Cancers 12, no. 6: 1380. https://doi.org/10.3390/cancers12061380
APA StyleJi, Y., Winter, L., Navarro, L., Ku, M.-C., Periquito, J. S., Pham, M., Hoffmann, W., Theune, L. E., Calderón, M., & Niendorf, T. (2020). Controlled Release of Therapeutics from Thermoresponsive Nanogels: A Thermal Magnetic Resonance Feasibility Study. Cancers, 12(6), 1380. https://doi.org/10.3390/cancers12061380