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Nanotechnology in Cancer Treatment

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (30 April 2019) | Viewed by 55938

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Special Issue Editors

Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, 1550 Orleans St., Baltimore, MD 21231, USA
Interests: magnetic fluid hyperthermia; hyperthermia; cancer nanomedicine; magnetic nanoparticles; nanoparticle-immune modulation
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The unique size of nanoparticles, in the 10–200 nm range, endows them with interesting and unique biological properties. They are small enough to penetrate most areas of the body and be ingested by cells, but large enough to carry multiple effector and targeting capabilities on their surface and within them. These unique capabilities have generated tremendous interest and effort to utilize nanoparticles of many sorts for cancer therapy and the field is moving very rapidly. The challenge of this field is that it lies at the intersection of multiple areas of extensive complexity, namely the inherent complexity of any cancer treatment and the variety of nanoparticle types that can be synthesized and component options that can be included, such as drugs, cytokines, targeting molecules, toxins, lipids and metallic particles. Further complexity involves the intersection of chemistry, engineering, cell biology, virology (viruses are nanoparticles), immunology and cancer biology, which all participate in this field. At this interface of multiple scientific fields are unique opportunities to develop new cancer therapies with specific physical attributes of nanoparticles. Publication of original research articles or reviews in this Special Issue will make an important contribution to developing nanotechnology based cancer therapies, and we invite submissions for this Special Issue.

Prof. Dr. Steven Fiering
Dr. Robert Ivkov
Guest Editors

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Keywords

  • Nanoparticles
  • Immunology
  • Nanoparticle characterization
  • Magnetic nanoparticles
  • Magnetic hyperthermia

Published Papers (11 papers)

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Research

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18 pages, 9969 KiB  
Article
Hepatic Cellular Distribution of Silica Nanoparticles by Surface Energy Modification
by A-Rang Lee, Kibeom Nam, Byeong Jun Lee, Seoung-Woo Lee, Su-Min Baek, Jun-Sun Bang, Seong-Kyoon Choi, Sang-Joon Park, Tae-Hwan Kim, Kyu-Shik Jeong, Dong Yun Lee and Jin-Kyu Park
Int. J. Mol. Sci. 2019, 20(15), 3812; https://doi.org/10.3390/ijms20153812 - 05 Aug 2019
Cited by 9 | Viewed by 3235
Abstract
The cellular distribution of silica nanoparticles (NPs) in the liver is not well understood. Targeting specific cells is one of the most important issues in NP-based drug delivery to improve delivery efficacy. In this context, the present study analyzed the relative cellular distribution [...] Read more.
The cellular distribution of silica nanoparticles (NPs) in the liver is not well understood. Targeting specific cells is one of the most important issues in NP-based drug delivery to improve delivery efficacy. In this context, the present study analyzed the relative cellular distribution pattern of silica NPs in the liver, and the effect of surface energy modification on NPs. Hydrophobic NP surface modification enhanced NP delivery to the liver and liver sinusoid fFendothelial cells (LSECs). Conversely, hydrophilic NP surface modification was commensurate with targeting hepatic stellate cells (HSCs) rather than other cell types. There was no notable difference in NP delivery to Kupffer cells or hepatocytes, regardless of hydrophilic or hydrophobic NP surface modification, suggesting that both the targeting of hepatocytes and evasion of phagocytosis by Kupffer cells are not associated with surface energy modification of silica NPs. This study provides useful information to target specific cell types using silica NPs, as well as to understand the relationship between NP surface energy and the NP distribution pattern in the liver, thereby helping to establish strategies for cell targeting using various NPs. Full article
(This article belongs to the Special Issue Nanotechnology in Cancer Treatment)
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20 pages, 4721 KiB  
Article
Optimisation of Folate-Mediated Liposomal Encapsulated Arsenic Trioxide for Treating HPV-Positive Cervical Cancer Cells In Vitro
by Anam Akhtar, Lucy Ghali, Scarlet Xiaoyan Wang, Celia Bell, Dong Li and Xuesong Wen
Int. J. Mol. Sci. 2019, 20(9), 2156; https://doi.org/10.3390/ijms20092156 - 30 Apr 2019
Cited by 18 | Viewed by 3312
Abstract
High-risk human papilloma virus (HPV) infection is directly associated with cervical cancer development. Arsenic trioxide (ATO), despite inducing apoptosis in HPV-infected cervical cancer cells in vitro, has been compromised by toxicity and poor pharmacokinetics in clinical trials. Therefore, to improve ATO’s therapeutic profile [...] Read more.
High-risk human papilloma virus (HPV) infection is directly associated with cervical cancer development. Arsenic trioxide (ATO), despite inducing apoptosis in HPV-infected cervical cancer cells in vitro, has been compromised by toxicity and poor pharmacokinetics in clinical trials. Therefore, to improve ATO’s therapeutic profile for HPV-related cancers, this study aims to explore the effects of length of ligand spacers of folate-targeted liposomes on the efficiency of ATO delivery to HPV-infected cells. Fluorescent ATO encapsulated liposomes with folic acid (FA) conjugated to two different PEG lengths (2000 Da and 5000 Da) were synthesised, and their cellular uptake was examined for HPV-positive HeLa and KB and HPV-negative HT-3 cells using confocal microscopy, flow cytometry, and spectrophotometer readings. Cellular arsenic quantification and anti-tumour efficacy was evaluated through inductively coupled plasma-mass spectrometry (ICP-MS) and cytotoxicity studies, respectively. Results showed that liposomes with a longer folic acid-polyethylene glycol (FA-PEG) spacer (5000 Da) displayed a higher efficiency in targeting folate receptor (FR) + HPV-infected cells without increasing any inherent cytotoxicity. Targeted liposomally delivered ATO also displayed superior selectivity and efficiency in inducing higher cell apoptosis in HPV-positive cells per unit of arsenic taken up than free ATO, in contrast to HT-3. These findings may hold promise in improving the management of HPV-associated cancers. Full article
(This article belongs to the Special Issue Nanotechnology in Cancer Treatment)
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14 pages, 3244 KiB  
Article
Modified Carboxyl-Terminated PAMAM Dendrimers as Great Cytocompatible Nano-Based Drug Delivery System
by Minh Thanh Vu, Long Giang Bach, Duy Chinh Nguyen, Minh Nhat Ho, Ngoc Hoi Nguyen, Ngoc Quyen Tran, Dai Hai Nguyen, Cuu Khoa Nguyen and Thai Thanh Hoang Thi
Int. J. Mol. Sci. 2019, 20(8), 2016; https://doi.org/10.3390/ijms20082016 - 24 Apr 2019
Cited by 36 | Viewed by 5661
Abstract
Polyamidoamine (PAMAM) dendrimers are extensively researched as potential drug delivery system thanks to their desirable features such as controlled and stable structures, and ease of functionalization onto their surface active groups. However, there have been concerns about the toxicity of full generation dendrimers [...] Read more.
Polyamidoamine (PAMAM) dendrimers are extensively researched as potential drug delivery system thanks to their desirable features such as controlled and stable structures, and ease of functionalization onto their surface active groups. However, there have been concerns about the toxicity of full generation dendrimers and risks of premature clearance from circulation, along with other physical drawbacks presented in previous formulations, including large particle sizes and low drug loading efficiency. In our study, carboxyl-terminated PAMAM dendrimer G3.5 was grafted with poly (ethylene glycol) methyl ether (mPEG) to be employed as a nano-based drug delivery system with great cytocompatibility for the delivery of carboplatin (CPT), a widely prescribed anticancer drug with strong side effects so that the drug will be effectively entrapped and not exhibit uncontrolled outflow from the open structure of unmodified PAMAM G3.5. The particles formed were spherical in shape and had the optimal size range (around 36 nm) that accommodates high drug entrapment efficiency. Surface charge was also determined to be almost neutral and the system was cytocompatible. In vitro release patterns over 24 h showed a prolonged CPT release compared to free drug, which correlated to the cytotoxicity assay on malignant cell lines showing the lack of anticancer effect of CPT/mPEG-G3.5 compared with CPT. Full article
(This article belongs to the Special Issue Nanotechnology in Cancer Treatment)
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25 pages, 5113 KiB  
Article
Challenges and Contradictions of Metal Nano-Particle Applications for Radio-Sensitivity Enhancement in Cancer Therapy
by Eva Pagáčová, Lenka Štefančíková, Franz Schmidt-Kaler, Georg Hildenbrand, Tomáš Vičar, Daniel Depeš, Jin-Ho Lee, Felix Bestvater, Sandrine Lacombe, Erika Porcel, Stéphane Roux, Frederik Wenz, Olga Kopečná, Iva Falková, Michael Hausmann and Martin Falk
Int. J. Mol. Sci. 2019, 20(3), 588; https://doi.org/10.3390/ijms20030588 - 30 Jan 2019
Cited by 34 | Viewed by 4401
Abstract
From the very beginnings of radiotherapy, a crucial question persists with how to target the radiation effectiveness into the tumor while preserving surrounding tissues as undamaged as possible. One promising approach is to selectively pre-sensitize tumor cells by metallic nanoparticles. However, though the [...] Read more.
From the very beginnings of radiotherapy, a crucial question persists with how to target the radiation effectiveness into the tumor while preserving surrounding tissues as undamaged as possible. One promising approach is to selectively pre-sensitize tumor cells by metallic nanoparticles. However, though the “physics” behind nanoparticle-mediated radio-interaction has been well elaborated, practical applications in medicine remain challenging and often disappointing because of limited knowledge on biological mechanisms leading to cell damage enhancement and eventually cell death. In the present study, we analyzed the influence of different nanoparticle materials (platinum (Pt), and gold (Au)), cancer cell types (HeLa, U87, and SKBr3), and doses (up to 4 Gy) of low-Linear Energy Transfer (LET) ionizing radiation (γ- and X-rays) on the extent, complexity and reparability of radiation-induced γH2AX + 53BP1 foci, the markers of double stand breaks (DSBs). Firstly, we sensitively compared the focus presence in nuclei during a long period of time post-irradiation (24 h) in spatially (three-dimensionally, 3D) fixed cells incubated and non-incubated with Pt nanoparticles by means of high-resolution immunofluorescence confocal microscopy. The data were compared with our preliminary results obtained for Au nanoparticles and recently published results for gadolinium (Gd) nanoparticles of approximately the same size (2–3 nm). Next, we introduced a novel super-resolution approach—single molecule localization microscopy (SMLM)—to study the internal structure of the repair foci. In these experiments, 10 nm Au nanoparticles were used that could be also visualized by SMLM. Altogether, the data show that different nanoparticles may or may not enhance radiation damage to DNA, so multi-parameter effects have to be considered to better interpret the radiosensitization. Based on these findings, we discussed on conclusions and contradictions related to the effectiveness and presumptive mechanisms of the cell radiosensitization by nanoparticles. We also demonstrate that SMLM offers new perspectives to study internal structures of repair foci with the goal to better evaluate potential differences in DNA damage patterns. Full article
(This article belongs to the Special Issue Nanotechnology in Cancer Treatment)
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19 pages, 9431 KiB  
Article
Development of Pectin-Type B Gelatin Polyelectrolyte Complex for Curcumin Delivery in Anticancer Therapy
by Fu-Ying Shih, Ih-Jen Su, Li-Lun Chu, Xiaojie Lin, Sheng-Chu Kuo, Yu-Chi Hou and Yi-Ting Chiang
Int. J. Mol. Sci. 2018, 19(11), 3625; https://doi.org/10.3390/ijms19113625 - 17 Nov 2018
Cited by 17 | Viewed by 4891
Abstract
Curcumin has been proven to be a potent agent in colon cancer treatment. However, its hydrophobicity and low oral bioavailability hampered its clinical application. These limitations could be improved through appropriate formulations such as using polyelectrolyte complexes (PECs). PECs were self-assembled with polycations [...] Read more.
Curcumin has been proven to be a potent agent in colon cancer treatment. However, its hydrophobicity and low oral bioavailability hampered its clinical application. These limitations could be improved through appropriate formulations such as using polyelectrolyte complexes (PECs). PECs were self-assembled with polycations and polyanions in polar solvents. In this study, a novel pectin-type B gelatin PEC was developed for use in curcumin formulation. At pH 4.0, natural polyanions pectin and polycations type B gelatin spontaneously formed PECs in ethanol/water solution, whereas under mimetic gastrointestinal tract (GI tract) conditions, at pH 2.0 and 8.0, pectin and type B gelatin were electrically neutralized, and the PECs swelled to allow payload release. After being transferred to pH 7.0 condition, as in the colon environment, PECs were internalized into colon carcinomas. Thus, pectin-type B gelatin PECs were successfully prepared, and their constituent ratio and drug-loading process were also optimized. The optimum particle size of the PECs was 264.0 ± 3.1 nm and they could swell as the zeta potential was altered at either pH 2.0 or 8.0. The optimum drug content and loading efficiency were 40% and 53%, respectively. At pH 2.0, curcumin was rapidly released from curcumin-loaded PECs, whereas at pH 8.0, curcumin-loaded PECs showed a sustained-release of curcumin. The bare PECs showed very low toxicity toward human normal cells, whereas curcumin-loaded PECs, after incubation at pH 2.0 for 2 h and at pH 8.0 for 4 h, induced cell cycle arrest and exhibited cytotoxic effect to HCT116 human colon cancer cells, even though these loaded PECs were pretreated with mimetic GI tract conditions. Our pectin-type B gelatin PECs were shown to be a promising oral formulation for curcumin delivery in anticancer therapy. Full article
(This article belongs to the Special Issue Nanotechnology in Cancer Treatment)
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27 pages, 9974 KiB  
Article
Chemotherapeutic Efficacy of Implantable Antineoplastic-Treatment Protocols in an Optimal Mouse Model for Human Ovarian Carcinoma Cell Targeting
by Jonathan M. Pantshwa, Khadija Rhoda, Sarah J. Clift, Priyamvada Pradeep, Yahya E. Choonara, Pradeep Kumar, Lisa C. Du Toit, Clement Penny and Viness Pillay
Int. J. Mol. Sci. 2018, 19(10), 3030; https://doi.org/10.3390/ijms19103030 - 04 Oct 2018
Cited by 7 | Viewed by 3269
Abstract
The present study aimed to design and develop a nanocomposite drug delivery system employing an antineoplastic-loaded antibody functionalized nanomicelle encapsulated within a Chitosan–Poly(vinylpyrrolidone)–Poly(N-isopropylacrylamide) (C–P–N) hydrogel to form an in situ forming implant (ISFI), responsive to temperature and pH for cancer cell-targeting [...] Read more.
The present study aimed to design and develop a nanocomposite drug delivery system employing an antineoplastic-loaded antibody functionalized nanomicelle encapsulated within a Chitosan–Poly(vinylpyrrolidone)–Poly(N-isopropylacrylamide) (C–P–N) hydrogel to form an in situ forming implant (ISFI), responsive to temperature and pH for cancer cell-targeting following intraperitoneal implantation. The optimum nanomicelle formulation was surface-functionalized with anti-MUC 16 (antibody) for the targeted delivery of methotrexate to human ovarian carcinoma (NIH:OVCAR-5) cells in Athymic nude mice that expressed MUC16, as a preferential form of intraperitoneal ovarian cancer (OC) chemotherapy. The cross-linked interpenetrating C–P–N hydrogel was synthesized for the preparation of an in situ-forming implant (ISFI). Subsequently, the ISFI was fabricated by encapsulating a nanocomposite comprising of anti-MUC16 (antibody) functionalized methotrexate (MTX)-loaded poly(N-isopropylacrylamide)-b-poly(aspartic acid) (PNIPAAm-b-PASP) nanomicelles (AF(MTX)NM’s) within the cross-linked C–P–N hydrogel. This strategy enabled specificity and increased the residence time of the nanomicelles at tumor sites over a period exceeding one month, enhancing uptake of drugs and preventing recurrence and chemo-resistance. Chemotherapeutic efficacy was tested on the optimal ovarian tumor-bearing Athymic nude mouse model and the results demonstrated tumor regression including reduction in mouse weight and tumor size, as well as a significant (p < 0.05) reduction in mucin 16 levels in plasma and ascitic fluid, and improved survival of mice after treatment with the experimental anti-MUC16/CA125 antibody-bound nanotherapeutic implant drug delivery system (ISFI) (p < 0.05). The study also concluded that ISFI could potentially be considered an important immuno-chemotherapeutic agent that could be employed in human clinical trials of advanced, and/or recurring, metastatic epithelial ovarian cancer (EOC). The development of this ISFI may circumvent the treatment flaws experienced with conventional systemic therapies, effectively manage recurrent disease and ultimately prolong disease-free intervals in ovarian cancer patients. Full article
(This article belongs to the Special Issue Nanotechnology in Cancer Treatment)
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18 pages, 3085 KiB  
Article
Lipid Nanoparticles Decorated with TNF-Related Aptosis-Inducing Ligand (TRAIL) Are More Cytotoxic than Soluble Recombinant TRAIL in Sarcoma
by Ana Gallego-Lleyda, Diego De Miguel, Alberto Anel and Luis Martinez-Lostao
Int. J. Mol. Sci. 2018, 19(5), 1449; https://doi.org/10.3390/ijms19051449 - 13 May 2018
Cited by 15 | Viewed by 4268
Abstract
Sarcomas are rare and heterogeneous cancers classically associated with a poor outcome. Sarcomas are 1% of the cancer but recent estimations indicate that sarcomas account for 2% of the estimated cancer-related deaths. Traditional treatment with surgery, radiotherapy, and chemotherapy has improved the outcome [...] Read more.
Sarcomas are rare and heterogeneous cancers classically associated with a poor outcome. Sarcomas are 1% of the cancer but recent estimations indicate that sarcomas account for 2% of the estimated cancer-related deaths. Traditional treatment with surgery, radiotherapy, and chemotherapy has improved the outcome for some types of sarcomas. However, novel therapeutic strategies to treat sarcomas are necessary. TNF-related apoptosis-inducing ligand (TRAIL) is a death ligand initially described as capable of inducing apoptosis on tumor cell while sparing normal cells. Only few clinical trials have used TRAIL-based treatments in sarcoma, but they show only low or moderate efficacy of TRAIL. Consequently, novel TRAIL formulations with an improved TRAIL bioactivity are necessary. Our group has developed a novel TRAIL formulation based on tethering this death ligand on a lipid nanoparticle surface (LUV-TRAIL) resembling the physiological secretion of TRAIL as a trasmembrane protein inserted into the membrane of exosomes. We have already demonstrated that LUV-TRAIL shows an improved cytotoxic activity when compared to soluble recombinant TRAIL both in hematological malignancies and epithelial-derived cancers. In the present study, we have tested LUV-TRAIL in several human sarcoma tumor cell lines with different sensitivity to soluble recombinant TRAIL, finding that LUV-TRAIL was more efficient than soluble recombinant TRAIL. Moreover, combined treatment of LUV-TRAIL with distinct drugs proved to be especially effective, sensitizing even more resistant cell lines to TRAIL. Full article
(This article belongs to the Special Issue Nanotechnology in Cancer Treatment)
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14 pages, 25004 KiB  
Article
Probing Interactions between AuNPs/AgNPs and Giant Unilamellar Vesicles (GUVs) Using Hyperspectral Dark-field Microscopy
by Anupama Bhat, Kewei Huan, Tiana Cooks, Hacene Boukari and Qi Lu
Int. J. Mol. Sci. 2018, 19(4), 1014; https://doi.org/10.3390/ijms19041014 - 28 Mar 2018
Cited by 12 | Viewed by 5482
Abstract
Noble metallic nanoparticles (NPs) such as gold and silver nanoparticles (AuNPs and AgNPs) have been shown to exhibit anti-tumor effect in anti-angiogenesis, photothermal and radio therapeutics. On the other hand, cell membranes are critical locales for specific targeting of cancerous cells. Therefore, NP-membrane [...] Read more.
Noble metallic nanoparticles (NPs) such as gold and silver nanoparticles (AuNPs and AgNPs) have been shown to exhibit anti-tumor effect in anti-angiogenesis, photothermal and radio therapeutics. On the other hand, cell membranes are critical locales for specific targeting of cancerous cells. Therefore, NP-membrane interactions need be studied at molecular level to help better understand the underlying physicochemical mechanisms for future applications in cancer nanotechnology. Herein, we report our study on the interactions between citrate stabilized colloidal AuNPs/AgNPs (10 nm in size) and giant unilamellar vesicles (GUVs) using hyperspectral dark-field microscopy. GUVs are large model vesicle systems well established for the study of membrane dynamics. GUVs used in this study were prepared with dimyristoyl phosphatidylcholine (DMPC) and doped with cholesterol at various molar concentrations. Both imaging and spectral results support that AuNPs and AgNPs interact very differently with GUVs, i.e., AuNPs tend to integrate in between the lipid bilayer and form a uniform golden-brown crust on vesicles, whereas AgNPs are bejeweled on the vesicle surface as isolated particles or clusters with much varied configurations. The more disruptive capability of AuNPs is hypothesized to be responsible for the formation of golden brown crusts in AuNP-GUV interaction. GUVs of 20 mol% CHOL:DMPC were found to be a most economical concentration for GUVs to achieve the best integrity and the least permeability, consistent with the finding from other phase studies of lipid mixture that the liquid-ordered domains have the largest area fraction of the entire membrane at around 20 mol% of cholesterol. Full article
(This article belongs to the Special Issue Nanotechnology in Cancer Treatment)
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15 pages, 8433 KiB  
Article
Targeting Glioblastoma Cells Expressing CD44 with Liposomes Encapsulating Doxorubicin and Displaying Chlorotoxin-IgG Fc Fusion Protein
by Hafizah Mahmud, Tomonari Kasai, Apriliana Cahya Khayrani, Mami Asakura, Aung Ko Ko Oo, Juan Du, Arun Vaidyanath, Samah El-Ghlban, Akifumi Mizutani, Akimasa Seno, Hiroshi Murakami, Junko Masuda and Masaharu Seno
Int. J. Mol. Sci. 2018, 19(3), 659; https://doi.org/10.3390/ijms19030659 - 26 Feb 2018
Cited by 26 | Viewed by 6507
Abstract
We recently have established a successful xenograft model of human glioblastoma cells by enriching hyaluronic acid-dependent spheroid-forming populations termed U251MG-P1 cells from U251MG cells. Since U251MG-P1 cells have been confirmed to express CD44 along with principal stemness marker genes, OCT3/4, SOX2, [...] Read more.
We recently have established a successful xenograft model of human glioblastoma cells by enriching hyaluronic acid-dependent spheroid-forming populations termed U251MG-P1 cells from U251MG cells. Since U251MG-P1 cells have been confirmed to express CD44 along with principal stemness marker genes, OCT3/4, SOX2, KLF4 and Nanog, this CD44 expressing population appeared to majorly consist of undifferentiated cells. Evaluating the sensitivity to anti-cancer agents, we found U251MG-P1 cells were sensitive to doxorubicin with IC50 at 200 nM. Although doxorubicin has serious side-effects, establishment of an efficient therapy targeting undifferentiated glioblastoma cell population is necessary. We previously designed a chlorotoxin peptide fused to human IgG Fc region without hinge sequence (M-CTX-Fc), which exhibited a stronger growth inhibitory effect on the glioblastoma cell line A172 than an original chlorotoxin peptide. Combining these results together, we designed M-CTX-Fc conjugated liposomes encapsulating doxorubicin and used U251MG-P1 cells as the target model in this study. The liposome modified with M-CTX-Fc was designed with a diameter of approximately 100–150 nm and showed high encapsulation efficiency, adequate loading capacity of anticancer drug, enhanced antitumor effects demonstrating increasing uptake into the cells in vitro; M-CTX-Fc-L-Dox shows great promise in its ability to suppress tumor growth in vivo and it could serve as a template for targeted delivery of other therapeutics. Full article
(This article belongs to the Special Issue Nanotechnology in Cancer Treatment)
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Review

Jump to: Research

20 pages, 3273 KiB  
Review
Multifunctional Cargo-Free Nanomedicine for Cancer Therapy
by Ying Wang, Pengfei Yang, Xinrui Zhao, Di Gao, Na Sun, Zhongmin Tian, Tianyou Ma and Zhe Yang
Int. J. Mol. Sci. 2018, 19(10), 2963; https://doi.org/10.3390/ijms19102963 - 28 Sep 2018
Cited by 23 | Viewed by 6604
Abstract
Nanocarriers encapsulating multiple chemotherapeutics are a promising strategy to achieve combinational chemotherapy for cancer therapy; however, they generally use exotic new carriers without therapeutic effect, which usually suffer from carrier-related toxicity issues, as well as having to pass extensive clinical trials to be [...] Read more.
Nanocarriers encapsulating multiple chemotherapeutics are a promising strategy to achieve combinational chemotherapy for cancer therapy; however, they generally use exotic new carriers without therapeutic effect, which usually suffer from carrier-related toxicity issues, as well as having to pass extensive clinical trials to be drug excipients before any clinical applications. Cargo-free nanomedicines, which are fabricated by drugs themselves without new excipients and possess nanoscale characteristics to realize favorable pharmacokinetics and intracellular delivery, have been rapidly developed and drawn much attention to cancer treatment. Herein, we discuss recent advances of cargo-free nanomedicines for cancer treatment. After a brief introduction to the major types of carrier-free nanomedicine, some representative applications of these cargo-free nanomedicines are discussed, including combination therapy, immunotherapy, as well as self-monitoring of drug release. More importantly, this review draws a brief conclusion and discusses the future challenges of cargo-free nanomedicines from our perspective. Full article
(This article belongs to the Special Issue Nanotechnology in Cancer Treatment)
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17 pages, 247 KiB  
Review
Targeting Macrophages as a Potential Therapeutic Intervention: Impact on Inflammatory Diseases and Cancer
by Mirco Ponzoni, Fabio Pastorino, Daniela Di Paolo, Patrizia Perri and Chiara Brignole
Int. J. Mol. Sci. 2018, 19(7), 1953; https://doi.org/10.3390/ijms19071953 - 04 Jul 2018
Cited by 108 | Viewed by 7145
Abstract
Macrophages, cells belonging to the innate immune system, present a high plasticity grade, being able to change their phenotype in response to environmental stimuli. They play central roles during development, homeostatic tissue processes, tissue repair, and immunity. Furthermore, it is recognized that macrophages [...] Read more.
Macrophages, cells belonging to the innate immune system, present a high plasticity grade, being able to change their phenotype in response to environmental stimuli. They play central roles during development, homeostatic tissue processes, tissue repair, and immunity. Furthermore, it is recognized that macrophages are involved in chronic inflammation and that they play central roles in inflammatory diseases and cancer. Due to their large involvement in the pathogenesis of several types of human diseases, macrophages are considered to be relevant therapeutic targets. Nanotechnology-based systems have attracted a lot of attention in this field, gaining a pivotal role as useful moieties to target macrophages in diseased tissues. Among the different approaches that can target macrophages, the most radical is represented by their depletion, commonly obtained by means of clodronate-containing liposomal formulations and/or depleting antibodies. These strategies have produced encouraging results in experimental mouse models. In this review, we focus on macrophage targeting, based on the results so far obtained in preclinical models of inflammatory diseases and cancer. Pros and cons of these therapeutic interventions will be highlighted. Full article
(This article belongs to the Special Issue Nanotechnology in Cancer Treatment)
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