Development of Novel Tumor-Targeting Nanoparticles

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Nanomedicine and Nanotechnology".

Deadline for manuscript submissions: closed (31 January 2023) | Viewed by 70593

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International Medical Center, University of Tsukuba Affiliated Hospital, Tsukuba 305-8576, Japan
Interests: cardiovascular immunology; ischemic insult; nanoparticle development; electron microscopy
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Radiation Oncology Unit, Department of Medical Sciences and Infectious Disease, Fondazione IRCCS, Policlinico San Matteo, Pavia, Italy
Interests: radiotherapy; radiation oncology; GU cancer; lung cancer; radiomics; immunotherapy
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Department of Neurosurgery, University of Tsukuba, Tsukuba, Tennodai, Japan
Interests: neurosurgery
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Special Issue Information

Dear Colleagues,

Despite the current coronavirus epidemic, cancer remains one of the most pressing problems of humankind, killing about 10 million people in 2020, according to statistics from the World Health Organization. As long as there are cancers that are fatal despite the use of the most modern treatments, there is a need to develop new drugs. Based on numerous published reports, nanoparticles (including liposomes, micelles, etc.) are capable of delivering much larger volumes of active components that stay sequestered in tumor cells for the time required for treatment, and with sufficient active targeting, nanoparticles would have enormous therapeutic potential. Therefore, innovating new tumor-targeting nanoparticles that can change the history of cancer treatment and save the lives of millions of people should be a priority. Therefore, we invite researchers engaged in such groundbreaking work to participate in a Special Issue of the journal by submitting their articles for publication in Pharmaceutics.

Dr. Bryan Mathis
Dr. Andrea Lancia
Dr. Alexander Zaboronok
Guest Editors

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Keywords

  • nanoparticles
  • nanoliposomes
  • nanomicelles
  • tumor targeting
  • drug delivery system
  • cancer
  • theranostics

Published Papers (23 papers)

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17 pages, 4918 KiB  
Article
Combined Treatment of Cancer Cells Using Allyl Palladium Complexes Bearing Purine-Based NHC Ligands and Molecules Targeting MicroRNAs miR-221-3p and miR-222-3p: Synergistic Effects on Apoptosis
by Chiara Tupini, Matteo Zurlo, Jessica Gasparello, Irene Lodi, Alessia Finotti, Thomas Scattolin, Fabiano Visentin, Roberto Gambari and Ilaria Lampronti
Pharmaceutics 2023, 15(5), 1332; https://doi.org/10.3390/pharmaceutics15051332 - 24 Apr 2023
Cited by 2 | Viewed by 1642
Abstract
Combined treatments employing lower concentrations of different drugs are used and studied to develop new and more effective anticancer therapeutic approaches. The combination therapy could be of great interest in the controlling of cancer. Regarding this, our research group has recently shown that [...] Read more.
Combined treatments employing lower concentrations of different drugs are used and studied to develop new and more effective anticancer therapeutic approaches. The combination therapy could be of great interest in the controlling of cancer. Regarding this, our research group has recently shown that peptide nucleic acids (PNAs) that target miR-221 are very effective and functional in inducing apoptosis of many tumor cells, including glioblastoma and colon cancer cells. Moreover, in a recent paper, we described a series of new palladium allyl complexes showing a strong antiproliferative activity on different tumor cell lines. The present study was aimed to analyze and validate the biological effects of the most active compounds tested, in combination with antagomiRNA molecules targeting two miRNAs, miR-221-3p and miR-222-3p. The obtained results show that a “combination therapy”, produced by combining the antagomiRNAs targeting miR-221-3p, miR-222-3p and the palladium allyl complex 4d, is very effective in inducing apoptosis, supporting the concept that the combination treatment of cancer cells with antagomiRNAs targeting a specific upregulated oncomiRNAs (in this study miR-221-3p and miR-222-3p) and metal-based compounds represents a promising therapeutic strategy to increase the efficacy of the antitumor protocol, reducing side effects at the same time. Full article
(This article belongs to the Special Issue Development of Novel Tumor-Targeting Nanoparticles)
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18 pages, 3774 KiB  
Article
Development and Characterization of Folic Acid-Conjugated Amodiaquine-Loaded Nanoparticles–Efficacy in Cancer Treatment
by Vineela Parvathaneni, Snehal K. Shukla and Vivek Gupta
Pharmaceutics 2023, 15(3), 1001; https://doi.org/10.3390/pharmaceutics15031001 - 20 Mar 2023
Cited by 5 | Viewed by 2558
Abstract
The objective of this study was to construct amodiaquine-loaded, folic acid-conjugated polymeric nanoparticles (FA-AQ NPs) to treat cancer that could be scaled to commercial production. In this study, folic acid (FA) was conjugated with a PLGA polymer followed by the formulation of drug-loaded [...] Read more.
The objective of this study was to construct amodiaquine-loaded, folic acid-conjugated polymeric nanoparticles (FA-AQ NPs) to treat cancer that could be scaled to commercial production. In this study, folic acid (FA) was conjugated with a PLGA polymer followed by the formulation of drug-loaded NPs. The results of the conjugation efficiency confirmed the conjugation of FA with PLGA. The developed folic acid-conjugated nanoparticles demonstrated uniform particle size distributions and had visible spherical shapes under transmission electron microscopy. The cellular uptake results suggested that FA modification could enhance the cellular internalization of nanoparticulate systems in non-small cell lung cancer, cervical, and breast cancer cell types. Furthermore, cytotoxicity studies showed the superior efficacy of FA-AQ NPs in different cancer cells such as MDAMB-231 and HeLA. FA-AQ NPs had better anti-tumor abilities demonstrated via 3D spheroid cell culture studies. Therefore, FA-AQ NPs could be a promising drug delivery system for cancer therapy. Full article
(This article belongs to the Special Issue Development of Novel Tumor-Targeting Nanoparticles)
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19 pages, 5861 KiB  
Article
Protein–Mineral Composite Particles with Logarithmic Dependence of Anticancer Cytotoxicity on Concentration of Montmorillonite Nanoplates with Adsorbed Cytochrome c
by Svetlana H. Hristova and Alexandar M. Zhivkov
Pharmaceutics 2023, 15(2), 386; https://doi.org/10.3390/pharmaceutics15020386 - 23 Jan 2023
Cited by 1 | Viewed by 1128
Abstract
Montmorillonite (MM) colloid nanoplates have high adsorption capacity due to their large size/thickness ratio, which allows them to be used as carriers for drug delivery. Upon adsorption of the mitochondrial protein cytochrome c (cytC) onto MM plates, the composite cytC–MM particles acquire anticancer [...] Read more.
Montmorillonite (MM) colloid nanoplates have high adsorption capacity due to their large size/thickness ratio, which allows them to be used as carriers for drug delivery. Upon adsorption of the mitochondrial protein cytochrome c (cytC) onto MM plates, the composite cytC–MM particles acquire anticancer properties because of the ability of cancer cells to phagocytize submicron particles (in contrast to the normal cells). In this way, exogenous cytC can be introduced into tumor cells, thereby triggering apoptosis—an irreversible cascade of biochemical reactions leading to cell death. In the present study, we investigated the physicochemical properties of cytC–MM particles as a function of the cytC concentration in the suspension, namely, the electrophoretic mobility, the mass increment of MM monoplates upon cytC adsorption, the ratio of the adsorbed to the free cytC in the bulk, the protein density on the MM’s surface, the number of cytC globules adsorbed on an MM monoplate, the concentration of cytC–MM composite particles in the suspension, and the dependence of cytotoxicity on the cytC–MM particle concentration. For this purpose, we used microelectrophoresis, static and electric light scattering, and a colon cancer cell culture to test the cytotoxic effects of the cytC–MM suspensions. The results show that the cytotoxicity depends linearly on the logarithm of the particle concentration in the cytC–MM suspension reaching 97%. Full article
(This article belongs to the Special Issue Development of Novel Tumor-Targeting Nanoparticles)
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14 pages, 1079 KiB  
Article
Astatine-211-Labeled Gold Nanoparticles for Targeted Alpha-Particle Therapy via Intravenous Injection
by Xuhao Huang, Kazuko Kaneda-Nakashima, Yuichiro Kadonaga, Kazuya Kabayama, Atsushi Shimoyama, Kazuhiro Ooe, Hiroki Kato, Atsushi Toyoshima, Atsushi Shinohara, Hiromitsu Haba, Yang Wang and Koichi Fukase
Pharmaceutics 2022, 14(12), 2705; https://doi.org/10.3390/pharmaceutics14122705 - 2 Dec 2022
Cited by 6 | Viewed by 2361
Abstract
Alpha-particle radiotherapy has gained considerable attention owing to its potent anti-cancer effect. 211At, with a relatively short half-life of 7.2 h, emits an alpha particle within a few cell diameters with high kinetic energy, which damages cancer cells with high biological effectiveness. [...] Read more.
Alpha-particle radiotherapy has gained considerable attention owing to its potent anti-cancer effect. 211At, with a relatively short half-life of 7.2 h, emits an alpha particle within a few cell diameters with high kinetic energy, which damages cancer cells with high biological effectiveness. In this study, we investigated the intravenous injection of 211At-labeled gold nanoparticles (AuNPs) for targeted alpha-particle therapy (TAT). Different kinds of surface-modified gold nanoparticles can be labeled with 211At in high radiochemical yield in 5 min, and no purification is necessary. The in vivo biodistribution results showed the accumulation of 5 nm 211At-AuNPs@mPEG at 2.25% injection dose per gram (% ID/g) in tumors within 3 h via the enhanced permeability and retention (EPR) effect. Additionally, we observed a long retention time in tumor tissues within 24 h. This is the first study to demonstrate the anti-tumor efficacy of 5 nm 211At-AuNPs@mPEG that can significantly suppress tumor growth in a pancreatic cancer model via intravenous administration. AuNPs are satisfactory carriers for 211At delivery, due to simple and efficient synthesis processes and high stability. The intravenous administration of 5 nm 211At-AuNPs@mPEG has a significant anti-tumor effect. This study provides a new framework for designing nanoparticles suitable for targeted alpha-particle therapy via intravenous injection. Full article
(This article belongs to the Special Issue Development of Novel Tumor-Targeting Nanoparticles)
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15 pages, 3275 KiB  
Article
Chlorin e6 Phospholipid Delivery System Featuring APN/CD13 Targeting Peptides: Cell Death Pathways, Cell Localization, In Vivo Biodistribution
by Yulia A. Tereshkina, Lyubov V. Kostryukova, Elena G. Tikhonova, Yulia Yu. Khudoklinova, Nadezhda A. Orlova, Alisa M. Gisina, Galina E. Morozevich, Pavel A. Melnikov and Vadim S. Pokrovsky
Pharmaceutics 2022, 14(10), 2224; https://doi.org/10.3390/pharmaceutics14102224 - 18 Oct 2022
Cited by 3 | Viewed by 1515
Abstract
We have previously designed a phospholipid delivery system for chlorin e6 to increase the efficacy of photodynamic therapy involving a second-generation photosensitizer. Further research into the matter led to double modification of the obtained nanoparticles with ligands exhibiting targeting and cell-penetrating effects: an [...] Read more.
We have previously designed a phospholipid delivery system for chlorin e6 to increase the efficacy of photodynamic therapy involving a second-generation photosensitizer. Further research into the matter led to double modification of the obtained nanoparticles with ligands exhibiting targeting and cell-penetrating effects: an NGR-containing peptide and heptaarginine (R7), respectively. This study investigated the cell death pathway on HT-1080 tumor cells after treatment with the proposed compositions: the chlorin e6 phospholipid composition and the two-peptide chlorin e6 phospholipid composition. It was demonstrated that most of the cells died by apoptosis. Colocalization analysis of chlorin e6 in the phospholipid composition with two peptides showed mitochondria are one of the targets of the photosensitizer. An HT-1080 tumor-bearing mouse model was used to evaluate the biodistribution of the drug in tumor, liver, and kidney tissues after administration of the study compositions in comparison with free chlorin e6. The photosensitizer mostly accumulated in the tumor tissue of mice administered the phospholipid compositions, and accumulation was increased 2-fold with the peptide-containing composition and approximately 1.5-fold with the unenhanced composition, as compared with free chlorin e6. The enhancement of the chlorin e6 phospholipid composition with targeting and cell-penetrating peptides was found to be effective both in vitro and in vivo. Full article
(This article belongs to the Special Issue Development of Novel Tumor-Targeting Nanoparticles)
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30 pages, 24863 KiB  
Article
Bioengineered Carboxymethylcellulose–Peptide Hybrid Nanozyme Cascade for Targeted Intracellular Biocatalytic–Magnetothermal Therapy of Brain Cancer Cells
by Alexandra A. P. Mansur, Sandhra M. Carvalho, Luiz Carlos A. Oliveira, Elaine Maria Souza-Fagundes, Zelia I. P. Lobato, Maria F. Leite and Herman S. Mansur
Pharmaceutics 2022, 14(10), 2223; https://doi.org/10.3390/pharmaceutics14102223 - 18 Oct 2022
Cited by 14 | Viewed by 2105
Abstract
Glioblastoma remains the most lethal form of brain cancer, where hybrid nanomaterials biofunctionalized with polysaccharide peptides offer disruptive strategies relying on passive/active targeting and multimodal therapy for killing cancer cells. Thus, in this research, we report for the first time the rational design [...] Read more.
Glioblastoma remains the most lethal form of brain cancer, where hybrid nanomaterials biofunctionalized with polysaccharide peptides offer disruptive strategies relying on passive/active targeting and multimodal therapy for killing cancer cells. Thus, in this research, we report for the first time the rational design and synthesis of novel hybrid colloidal nanostructures composed of gold nanoparticles stabilized by trisodium citrate (AuNP@TSC) as the oxidase-like nanozyme, coupled with cobalt-doped superparamagnetic iron oxide nanoparticles stabilized by carboxymethylcellulose ligands (Co-MION@CMC) as the peroxidase-like nanozyme. They formed inorganic–inorganic dual-nanozyme systems functionalized by a carboxymethylcellulose biopolymer organic shell, which can trigger a biocatalytic cascade reaction in the cancer tumor microenvironment for the combination of magnetothermal–chemodynamic therapy. These nanoassemblies were produced through a green aqueous process under mild conditions and chemically biofunctionalized with integrin-targeting peptide (iRDG), creating bioengineered nanocarriers. The results demonstrated that the oxidase-like nanozyme (AuNP) was produced with a crystalline face-centered cubic nanostructure, spherical morphology (diameter = 16 ± 3 nm), zeta potential (ZP) of −50 ± 5 mV, and hydrodynamic diameter (DH) of 15 ± 1 nm. The peroxide-like nanostructure (POD, Co-MION@CMC) contained an inorganic crystalline core of magnetite and had a uniform spherical shape (2R = 7 ± 1 nm) which, summed to the contribution of the CMC shell, rendered a hydrodynamic diameter of 45 ± 4 nm and a negative surface charge (ZP = −41 ± 5 mV). Upon coupling both nanozymes, water-dispersible colloidal supramolecular vesicle-like organic–inorganic nanostructures were produced (AuNP//Co-MION@CMC, ZP = −45 ± 4 mV and DH = 28 ± 3 nm). They confirmed dual-nanozyme cascade biocatalytic activity targeted by polymer–peptide conjugates (AuNP//Co-MION@CMC_iRGD, ZP = −29 ± 3 mV and DH = 60 ± 4 nm) to kill brain cancer cells (i.e., bioenergy “starvation” by glucose deprivation and oxidative stress through reactive oxygen species generation), which was boosted by the magneto-hyperthermotherapy effect when submitted to the alternating magnetic field (i.e., induced local thermal stress by “nanoheaters”). This groundwork offers a wide avenue of opportunities to develop innovative theranostic nanoplatforms with multiple integrated functionalities for fighting cancer and reducing the harsh side effects of conventional chemotherapy. Full article
(This article belongs to the Special Issue Development of Novel Tumor-Targeting Nanoparticles)
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18 pages, 4067 KiB  
Article
Quantifying Radiosensitization of PSMA-Targeted Gold Nanoparticles on Prostate Cancer Cells at Megavoltage Radiation Energies by Monte Carlo Simulation and Local Effect Model
by Ryder M. Schmidt, Daiki Hara, Jorge D. Vega, Marwan B. Abuhaija, Wensi Tao, Nesrin Dogan, Alan Pollack, John C. Ford and Junwei Shi
Pharmaceutics 2022, 14(10), 2205; https://doi.org/10.3390/pharmaceutics14102205 - 17 Oct 2022
Cited by 8 | Viewed by 2146
Abstract
Active targeting gold nanoparticles (AuNPs) are a very promising avenue for cancer treatment with many publications on AuNP mediated radiosensitization at kilovoltage (kV) photon energies. However, uncertainty on the effectiveness of AuNPs under clinically relevant megavoltage (MV) radiation energies hinders the clinical translation [...] Read more.
Active targeting gold nanoparticles (AuNPs) are a very promising avenue for cancer treatment with many publications on AuNP mediated radiosensitization at kilovoltage (kV) photon energies. However, uncertainty on the effectiveness of AuNPs under clinically relevant megavoltage (MV) radiation energies hinders the clinical translation of AuNP-assisted radiation therapy (RT) paradigm. The aim of this study was to investigate radiosensitization mediated by PSMA-targeted AuNPs irradiated by a 6 MV radiation beam at different depths to explore feasibility of AuNP-assisted prostate cancer RT under clinically relevant conditions. PSMA-targeted AuNPs (PSMA-AuNPs) were synthesized by conjugating PSMA antibodies onto PEGylated AuNPs through EDC/NHS chemistry. Confocal fluorescence microscopy was used to verify the active targeting of the developed PSMA-AuNPs. Transmission electron microscopy (TEM) was used to demonstrate the intracellular biodistribution of PSMA-AuNPs. LNCaP prostate cancer cells treated with PSMA-AuNPs were irradiated on a Varian 6 MV LINAC under varying depths (2.5 cm, 10 cm, 20 cm, 30 cm) of solid water. Clonogenic assays were carried out to determine the in vitro cell survival fractions. A Monte Carlo (MC) model developed on TOPAS platform was then employed to determine the nano-scale radial dose distribution around AuNPs, which was subsequently used to predict the radiation dose response of LNCaP cells treated with AuNPs. Two different cell models, with AuNPs located within the whole cell or only in the cytoplasm, were used to assess how the intracellular PSMA-AuNP biodistribution impacts the prostate cancer radiosensitization. Then, MC-based microdosimetry was combined with the local effect model (LEM) to calculate cell survival fraction, which was benchmarked against the in vitro clonogenic assays at different depths. In vitro clonogenic assay of LNCaP cells demonstrated the depth dependence of AuNP radiosensitization under clinical megavoltage beams, with sensitization enhancement ratio (SER) of 1.14 ± 0.03 and 1.55 ± 0.05 at 2.5 cm depth and 30 cm depth, respectively. The MC microdosimetry model showed the elevated percent of low-energy photons in the MV beams at greater depth, consequently resulting in increased dose enhancement ratio (DER) of AuNPs with depth. The AuNP-induced DER reached ~5.7 and ~8.1 at depths of 2.5 cm and 30 cm, respectively. Microdosimetry based LEM accurately predicted the cell survival under 6 MV beams at different depths, for the cell model with AuNPs placed only in the cell cytoplasm. TEM results demonstrated the distribution of PSMA-AuNPs in the cytoplasm, confirming the accuracy of MC microdosimetry based LEM with modelled AuNPs distributed within the cytoplasm. We conclude that AuNP radiosensitization can be achieved under megavoltage clinical radiotherapy energies with a dependence on tumor depth. Furthermore, the combination of Monte Carlo microdosimetry and LEM will be a valuable tool to assist with developing AuNP-aided radiotherapy paradigm and drive clinical translation. Full article
(This article belongs to the Special Issue Development of Novel Tumor-Targeting Nanoparticles)
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12 pages, 7170 KiB  
Article
Tumor-Specific Monomethyl Auristatin E (MMAE) Prodrug Nanoparticles for Safe and Effective Chemotherapy
by Hanhee Cho, Man Kyu Shim, Yujeong Moon, Sukyung Song, Jinseong Kim, Jiwoong Choi, Jeongrae Kim, Youngjoo Lee, Jung Yeon Park, Yongju Kim, Cheol-Hee Ahn, Mi Ra Kim, Hong Yeol Yoon and Kwangmeyung Kim
Pharmaceutics 2022, 14(10), 2131; https://doi.org/10.3390/pharmaceutics14102131 - 7 Oct 2022
Cited by 7 | Viewed by 3061
Abstract
A prodrug is bioreversible medication that is specifically converted to the active drugs by enzymes overexpressed in the tumor microenvironment, which can considerably reduce the chemotherapy-induced side effects. However, prodrug strategies usually have low antitumor efficacy compared to free drugs by delayed drug [...] Read more.
A prodrug is bioreversible medication that is specifically converted to the active drugs by enzymes overexpressed in the tumor microenvironment, which can considerably reduce the chemotherapy-induced side effects. However, prodrug strategies usually have low antitumor efficacy compared to free drugs by delayed drug release. This is because they need time to be activated by enzymatic cleavage and they also cannot be fully recovered to the active drugs. Therefore, highly potent anticancer drug should be considered to expect a sufficient antitumor efficacy. Herein, we propose tumor-specific monomethyl auristatin E (MMAE) prodrug nanoparticles for safe and effective chemotherapy. The cathepsin B-specific cleavable FRRG peptide and MMAE are chemically conjugated via one-step simple synthetic chemistry. The resulting FRRG-MMAE molecules form stable nanoparticles without any additional carrier materials by hydrophobic interaction-derived aggregations. The FRRG-MMAE nanoparticles efficiently accumulate within the tumor tissues owing to the enhanced permeability and retention (EPR) effect and inhibit the tubulin polymerization by releasing free MMAE in the cathepsin B-overexpressed tumor cells. In contrast, FRRG-MMAE nanoparticles maintain a non-toxic inactive state in the normal tissues owing to innately low cathepsin B expression, thereby reducing MMAE-related severe toxicity. Collectively, this study provides a promising approach for safe and effective chemotherapy via MMAE-based prodrug nanoparticles, which may open new avenues for advanced drug design for translational nanomedicine. Full article
(This article belongs to the Special Issue Development of Novel Tumor-Targeting Nanoparticles)
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16 pages, 3307 KiB  
Article
Lung Cancer Targeted Chemoradiotherapy via Dual-Stimuli Responsive Biodegradable Core-Shell Nanoparticles
by Roshni Iyer, Harish Ramachandramoorthy, Trinh Nguyen, Cancan Xu, Huikang Fu, Tanviben Kotadia, Benjamin Chen, Yi Hong, Debabrata Saha and Kytai Truong Nguyen
Pharmaceutics 2022, 14(8), 1525; https://doi.org/10.3390/pharmaceutics14081525 - 22 Jul 2022
Cited by 8 | Viewed by 2062
Abstract
Lung cancer is one of the major causes of cancer-related deaths worldwide, primarily because of the limitations of conventional clinical therapies such as chemotherapy and radiation therapy. Side effects associated with these treatments have made it essential for new modalities, such as tumor [...] Read more.
Lung cancer is one of the major causes of cancer-related deaths worldwide, primarily because of the limitations of conventional clinical therapies such as chemotherapy and radiation therapy. Side effects associated with these treatments have made it essential for new modalities, such as tumor targeting nanoparticles that can provide cancer specific therapies. In this research, we have developed novel dual-stimuli nanoparticles (E-DSNPs), comprised of two parts; (1) Core: responsive to glutathione as stimuli and encapsulating Cisplatin (a chemo-drug), and (2) Shell: responsive to irradiation as stimuli and containing NU7441 (a radiation sensitizer). The targeting moieties on these nanoparticles are Ephrin transmembrane receptors A2 (EphA2) that are highly expressed on the surfaces of lung cancer cells. These nanoparticles were then evaluated for their enhanced targeting and therapeutic efficiency against lung cancer cell lines. E-DSNPs displayed very high uptake by lung cancer cells compared to healthy lung epithelial cells. These nanoparticles also demonstrated a triggered release of both drugs against respective stimuli and a subsequent reduction in in vitro cancer cell survival fraction compared to free drugs of equivalent concentration (survival fraction of about 0.019 and 0.19, respectively). Thus, these nanoparticles could potentially pave the path to targeted cancer therapy, while overcoming the side effects of conventional clinical therapies. Full article
(This article belongs to the Special Issue Development of Novel Tumor-Targeting Nanoparticles)
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17 pages, 4374 KiB  
Article
Mono and Multiple Tumor-Targeting Ligand-Coated Ultrasmall Gadolinium Oxide Nanoparticles: Enhanced Tumor Imaging and Blood Circulation
by Son Long Ho, Huan Yue, Sangyeol Lee, Tirusew Tegafaw, Mohammad Yaseen Ahmad, Shuwen Liu, Abdullah Khamis Ali Al Saidi, Dejun Zhao, Ying Liu, Sung-Wook Nam, Kwon Seok Chae, Yongmin Chang and Gang Ho Lee
Pharmaceutics 2022, 14(7), 1458; https://doi.org/10.3390/pharmaceutics14071458 - 12 Jul 2022
Cited by 4 | Viewed by 2586
Abstract
Hydrophilic and biocompatible PAA-coated ultrasmall Gd2O3 nanoparticles (davg = 1.7 nm) were synthesized and conjugated with tumor-targeting ligands, i.e., cyclic arginylglycylaspartic acid (cRGD) and/or folic acid (FA). FA-PAA-Gd2O3 and cRGD/FA-PAA-Gd2O3 nanoparticles were successfully [...] Read more.
Hydrophilic and biocompatible PAA-coated ultrasmall Gd2O3 nanoparticles (davg = 1.7 nm) were synthesized and conjugated with tumor-targeting ligands, i.e., cyclic arginylglycylaspartic acid (cRGD) and/or folic acid (FA). FA-PAA-Gd2O3 and cRGD/FA-PAA-Gd2O3 nanoparticles were successfully applied in U87MG tumor-bearing mice for tumor imaging using T1 magnetic resonance imaging (MRI). cRGD/FA-PAA-Gd2O3 nanoparticles with multiple tumor-targeting ligands exhibited higher contrasts at the tumor site than FA-PAA-Gd2O3 nanoparticles with mono tumor-targeting ligands. In addition, the cRGD/FA-PAA-Gd2O3 nanoparticles exhibited higher contrasts in all organs, especially the aorta, compared with those of the FA-PAA-Gd2O3 nanoparticles, because of the blood cell hitchhiking effect of cRGD in the cRGD/FA-PAA-Gd2O3 nanoparticles, which prolonged their circulation in the blood. Full article
(This article belongs to the Special Issue Development of Novel Tumor-Targeting Nanoparticles)
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14 pages, 2470 KiB  
Article
The Potential of Cell-Penetrating Peptides for mRNA Delivery to Cancer Cells
by Yelee Kim, Hyosuk Kim, Eun Hye Kim, Hochung Jang, Yeongji Jang, Sung-Gil Chi, Yoosoo Yang and Sun Hwa Kim
Pharmaceutics 2022, 14(6), 1271; https://doi.org/10.3390/pharmaceutics14061271 - 15 Jun 2022
Cited by 24 | Viewed by 4804
Abstract
In vitro transcribed mRNA for the synthesis of any given protein has shown great potential in cancer gene therapy, especially in cancer vaccines for immunotherapy. To overcome physiological barriers, such as rapid degradation by enzymatic attack and poor cellular uptake due to their [...] Read more.
In vitro transcribed mRNA for the synthesis of any given protein has shown great potential in cancer gene therapy, especially in cancer vaccines for immunotherapy. To overcome physiological barriers, such as rapid degradation by enzymatic attack and poor cellular uptake due to their large size and hydrophilic properties, many delivery carriers for mRNAs are being investigated for improving the bioavailability of mRNA. Recently, cell-penetrating peptides (CPPs) have received attention as promising tools for gene delivery. In terms of their biocompatibility and the ability to target specific cells with the versatility of peptide sequences, they may provide clues to address the challenges of conventional delivery systems for cancer mRNA delivery. In this study, optimal conditions for the CPP/mRNA complexes were identified in terms of complexation capacity and N/P ratio, and protection against RNase was confirmed. When cancer cells were treated at a concentration of 6.8 nM, which could deliver the highest amount of mRNA without toxicity, the amphipathic CPP/mRNA complexes with a size less than 200 nm showed high cellular uptake and protein expression. With advances in our understanding of CPPs, CPPs designed to target tumor tissues will be promising for use in developing a new class of mRNA delivery vehicles in cancer therapy. Full article
(This article belongs to the Special Issue Development of Novel Tumor-Targeting Nanoparticles)
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25 pages, 5141 KiB  
Article
The Effect of Encapsulated Apigenin Nanoparticles on HePG-2 Cells through Regulation of P53
by Mayada Mohamed Mabrouk Zayed, Heba A. Sahyon, Nemany A. N. Hanafy and Maged A. El-Kemary
Pharmaceutics 2022, 14(6), 1160; https://doi.org/10.3390/pharmaceutics14061160 - 29 May 2022
Cited by 26 | Viewed by 3063
Abstract
Apigenin (Ap) is one of the most important natural flavonoids that has potent anticancer activity. This study was designed, for the first time, to load Ap into chitosan to improve its hydrophobicity and then it was coated with albumin-folic acid to increase its [...] Read more.
Apigenin (Ap) is one of the most important natural flavonoids that has potent anticancer activity. This study was designed, for the first time, to load Ap into chitosan to improve its hydrophobicity and then it was coated with albumin-folic acid to increase its stability and bioavailability and to target cancer cells. The newly developed encapsulated Ap (Ap-CH-BSA-FANPs) was characterized and tested in vitro. The zeta potential of −17.0 mV was within the recommended range (−30 mV to +30 mV), indicating that encapsulated apigenin would not quickly settle and would be suspended. The in vitro results proved the great anticancer activity of the encapsulated apigenin on HePG-2 cells compared to pure Ap. The treated HePG-2 cells with Ap-CH-BSA-FANPs demonstrated the induction of apoptosis by increasing p53 gene expression, arresting the cell cycle, increasing caspase-9 levels, and decreasing both the MMP9 gene and Bcl-2 protein expression levels. Moreover, the higher antioxidant activity of the encapsulated apigenin treatment was evident through increasing SOD levels and decreasing the CAT concentration. In conclusion, the Ap-CH-BSA-FANPs were easy to produce with low coast, continued drug release, good loading capacity, high solubility in physiological pH, and were more stable than the formerly Ap-loaded liposomes or PLGA. Moreover, Ap-CH-BSA-FANPs may be a promising chemotherapeutic agent in the treatment of HCC. Full article
(This article belongs to the Special Issue Development of Novel Tumor-Targeting Nanoparticles)
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18 pages, 8666 KiB  
Article
Polymer-Stabilized Elemental Boron Nanoparticles for Boron Neutron Capture Therapy: Initial Irradiation Experiments
by Alexander Zaboronok, Polina Khaptakhanova, Sergey Uspenskii, Raman Bekarevich, Ludmila Mechetina, Olga Volkova, Bryan J. Mathis, Vladimir Kanygin, Eiichi Ishikawa, Anna Kasatova, Dmitrii Kasatov, Ivan Shchudlo, Tatiana Sycheva, Sergey Taskaev and Akira Matsumura
Pharmaceutics 2022, 14(4), 761; https://doi.org/10.3390/pharmaceutics14040761 - 31 Mar 2022
Cited by 12 | Viewed by 3335
Abstract
Sufficient boron-10 isotope (10B) accumulation by tumor cells is one of the main requirements for successful boron neutron capture therapy (BNCT). The inability of the clinically registered 10B-containing borophenylalanine (BPA) to maintain a high boron tumor concentration during neutron irradiation [...] Read more.
Sufficient boron-10 isotope (10B) accumulation by tumor cells is one of the main requirements for successful boron neutron capture therapy (BNCT). The inability of the clinically registered 10B-containing borophenylalanine (BPA) to maintain a high boron tumor concentration during neutron irradiation after a single injection has been partially solved by its continuous infusion; however, its lack of persistence has driven the development of new compounds that overcome the imperfections of BPA. We propose using elemental boron nanoparticles (eBNPs) synthesized by cascade ultrasonic dispersion and destruction of elemental boron microparticles and stabilized with hydroxyethylcellulose (HEC) as a core component of a novel boron drug for BNCT. These HEC particles are stable in aqueous media and show no apparent influence on U251, U87, and T98G human glioma cell proliferation without neutron beam irradiation. In BNCT experiments, cells incubated with eBNPs or BPA at an equivalent concentration of 40 µg 10B/mL for 24 h or control cells without boron were irradiated at an accelerator-based neutron source with a total fluence of thermal and epithermal neutrons of 2.685, 5.370, or 8.055 × 1012/cm2. The eBNPs significantly reduced colony-forming capacity in all studied cells during BNCT compared to BPA, verified by cell-survival curves fit to the linear-quadratic model and calculated radiobiological parameters, though the effect of both compounds differed depending on the cell line. The results of our study warrant further tumor targeting-oriented modifications of synthesized nanoparticles and subsequent in vivo BNCT experiments. Full article
(This article belongs to the Special Issue Development of Novel Tumor-Targeting Nanoparticles)
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24 pages, 4716 KiB  
Article
Increased Targeting Area in Tumors by Dual-Ligand Modification of Liposomes with RGD and TAT Peptides
by Mohamadreza Amin, Mercedeh Mansourian, Peter C. Burgers, Bahareh Amin, Mahmoud Reza Jaafari and Timo L. M. ten Hagen
Pharmaceutics 2022, 14(2), 458; https://doi.org/10.3390/pharmaceutics14020458 - 21 Feb 2022
Cited by 10 | Viewed by 2916
Abstract
Modification with polyethylene glycol (PEGylation) and the use of rigid phospholipids drastically improve the pharmacokinetics of chemotherapeutics and result in more manageable or reduced side-effects. A major drawback is retarded cellular delivery of content, which, along with tumor heterogeneity, are the two main [...] Read more.
Modification with polyethylene glycol (PEGylation) and the use of rigid phospholipids drastically improve the pharmacokinetics of chemotherapeutics and result in more manageable or reduced side-effects. A major drawback is retarded cellular delivery of content, which, along with tumor heterogeneity, are the two main obstacles against tumor targeting. To enhance cellular delivery and reach a bigger area of a tumor, we designed liposomes decorated with two ligands: one for targeting tumor vasculature via a cyclic-pentapeptide containing arginine-glycine-aspartic acid (RGD), which impacts tumor independent of passive accumulation inside tumors, and one for extravascular targeting of tumor cells via a cell-penetrating peptide derived from human immunodeficiency virus type 1 transactivator of transcription (TAT). Liposomes with different ligand combinations were prepared and compared with respect to performance in targeting. Intravital imaging illustrates the heterogeneous behavior of RGD-liposomes in both intravascular and extravascular distribution, whereas TAT-liposomes exhibit a predictable extravascular localization but no intravascular targeting. Dual-ligand modification results in enhanced vascular targeting and a predictable extravascular behavior that improves the therapeutic efficacy of doxorubicin-loaded liposomes but also an augmented clearance rate of liposomes. However, the dual-modified liposome could be a great candidate for targeted delivery of non-toxic payloads or contrast agents for therapeutic or diagnostic purposes. Here we show that the combination of vascular-specific and tumor cell-specific ligands in a liposomal system is beneficial in bypassing the heterogeneous expression of tumor-specific markers. Full article
(This article belongs to the Special Issue Development of Novel Tumor-Targeting Nanoparticles)
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14 pages, 1763 KiB  
Article
The Impact of Fullerenes as Doxorubicin Nano-Transporters on Metallothionein and Superoxide Dismutase Status in MCF-10A Cells
by Natalia Zaręba, Klaudia Więcławik, Rene Kizek, Bozena Hosnedlova and Marta Kepinska
Pharmaceutics 2022, 14(1), 102; https://doi.org/10.3390/pharmaceutics14010102 - 2 Jan 2022
Cited by 5 | Viewed by 1969
Abstract
This study aimed to synthesise C60–DOX complexes followed by the analysis of their effect on the concentration of metallothionein (MT) as a non-enzymatic antioxidant and on the concentration and activity of superoxide dismutase (SOD) as an antioxidant enzyme in healthy human [...] Read more.
This study aimed to synthesise C60–DOX complexes followed by the analysis of their effect on the concentration of metallothionein (MT) as a non-enzymatic antioxidant and on the concentration and activity of superoxide dismutase (SOD) as an antioxidant enzyme in healthy human mammary MCF-10A cells. Dynamic light scattering and electrophoretic light scattering were used to establish the size and zeta potential of the complexes. The MT and SOD concentrations were determined using the ELISA method; SOD activity was determined by tetrazolium salt reduction inhibition. Lower MT concentration following exposure of cells to both DOX and C60 fullerene compared to the control sample was found. However, the concentration of this protein increased as a consequence of the C60–DOX complexes action on MCF-10A cells compared to the control. C60 used alone did not affect the concentration and activity of SOD in MCF-10A cells. Application of free DOX did not activate cellular antioxidant defence in the form of an increase in SOD concentration or its activity. In contrast treatment of cells with the C60–DOX complex resulted in a decrease in SOD1 concentration and a significant increase in SOD activity compared to cells treated with free DOX, C60 and control. Thus, it was found that C60–DOX complexes showed potential for protective effects against DOX-induced toxicity to MCF-10A cells. Full article
(This article belongs to the Special Issue Development of Novel Tumor-Targeting Nanoparticles)
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16 pages, 2257 KiB  
Article
ICAM-1 Targeted Drug Combination Nanoparticles Enhanced Gemcitabine-Paclitaxel Exposure and Breast Cancer Suppression in Mouse Models
by Linxi Zhu, Qingxin Mu, Jesse Yu, James I. Griffin, Xiaolin Xu and Rodney J. Y. Ho
Pharmaceutics 2022, 14(1), 89; https://doi.org/10.3390/pharmaceutics14010089 - 31 Dec 2021
Cited by 10 | Viewed by 2487
Abstract
Despite the availability of molecularly targeted treatments such as antibodies and small molecules for human epidermal growth factor receptor 2 (HER2), hormone receptor (HR), and programmed death-ligand 1 (PD-L1), limited treatment options are available for advanced metastatic breast cancer (MBC), which constitutes ~90% [...] Read more.
Despite the availability of molecularly targeted treatments such as antibodies and small molecules for human epidermal growth factor receptor 2 (HER2), hormone receptor (HR), and programmed death-ligand 1 (PD-L1), limited treatment options are available for advanced metastatic breast cancer (MBC), which constitutes ~90% mortality. Many of these monotherapies often lead to drug resistance. Novel MBC-targeted drug-combination therapeutic approaches that may reduce resistance are urgently needed. We investigated intercellular adhesion molecule-1 (ICAM-1), which is abundant in MBC, as a potential target to co-localize two current drug combinations, gemcitabine (G) and paclitaxel (T), assembled in a novel drug-combination nanoparticle (GT DcNP) form. With an ICAM-1-binding peptide (referred to as LFA1-P) coated on GT DcNPs, we evaluated the role of the LFA1-P density in breast cancer cell localization in vitro and in vivo. We found that 1–2% LFA1-P peptide incorporated on GT DcNPs provided optimal cancer cell binding in vitro with ~4× enhancement compared to non-peptide GT DcNPs. The in vivo probing of GT DcNPs labeled with a near-infrared marker, indocyanine green, in mice by bio-imaging and G and T analyses indicated LFA1-P enhanced drug and GT DcNP localization in breast cancer cells. The target/healthy tissue (lung/gastrointestinal (GI)) ratio of particles increased by ~60× compared to the non-ligand control. Collectively, these data indicated that LFA1 on GT DcNPs may provide ICAM-1-targeted G and T drug combination delivery to advancing MBC cells found in lung tissues. As ICAM-1 is generally expressed even in breast cancers that are triple-negative phenotypes, which are unresponsive to inhibitors of nuclear receptors or HER2/estrogen receptor (ER) agents, ICAM-1-targeted LFA1-P-coated GT DcNPs should be considered for clinical development to improve therapeutic outcomes of MBCs. Full article
(This article belongs to the Special Issue Development of Novel Tumor-Targeting Nanoparticles)
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29 pages, 11920 KiB  
Article
Anticancer Potential of Green Synthesized Silver Nanoparticles of the Soft Coral Cladiella pachyclados Supported by Network Pharmacology and In Silico Analyses
by Hani A. Alhadrami, Heba Alkhatabi, Fahad H. Abduljabbar, Usama Ramadan Abdelmohsen and Ahmed M. Sayed
Pharmaceutics 2021, 13(11), 1846; https://doi.org/10.3390/pharmaceutics13111846 - 3 Nov 2021
Cited by 9 | Viewed by 3376
Abstract
Cladiella-derived natural products have shown promising anticancer properties against many human cancer cell lines. In the present investigation, we found that an ethyl acetate extract of Cladiella pachyclados (CE) collected from the Red Sea could inhibit the human breast cancer (BC) cells [...] Read more.
Cladiella-derived natural products have shown promising anticancer properties against many human cancer cell lines. In the present investigation, we found that an ethyl acetate extract of Cladiella pachyclados (CE) collected from the Red Sea could inhibit the human breast cancer (BC) cells (MCF and MDA-MB-231) in vitro (IC50 24.32 ± 1.1 and 9.55 ± 0.19 µg/mL, respectively). The subsequent incorporation of the Cladiella extract into the green synthesis of silver nanoparticles (AgNPs) resulted in significantly more activity against both cancer cell lines (IC50 5.62 ± 0.89 and 1.72 ± 0.36, respectively); the efficacy was comparable to that of doxorubicin with much-enhanced selectivity. To explore the mode of action of this extract, various in silico and network-pharmacology-based analyses were performed in the light of the LC-HRESIMS-identified compounds in the CE extract. Firstly, using two independent machine-learning-based prediction software platforms, most of the identified compounds in CE were predicted to inhibit both MCF7 and MDA-MB-231. Moreover, they were predicted to have low toxicity towards normal cell lines. Secondly, approximately 242 BC-related molecular targets were collected from various databases and used to construct a protein–protein interaction (PPI) network, which revealed the most important molecular targets and signaling pathways in the pathogenesis of BC. All the identified compounds in the extract were then subjected to inverse docking against all proteins hosted in the Protein Data bank (PDB) to discover the BC-related proteins that these compounds can target. Approximately, 10.74% of the collected BC-related proteins were potential targets for 70% of the compounds identified in CE. Further validation of the docking results using molecular dynamic simulations (MDS) and binding free energy calculations revealed that only 2.47% of the collected BC-related proteins could be targeted by 30% of the CE-derived compounds. According to docking and MDS experiments, protein-pathway and compound-protein interaction networks were constructed to determine the signaling pathways that the CE compounds could influence. This paper highlights the potential of marine natural products as effective anticancer agents and reports the discovery of novel anti-breast cancer AgNPs. Full article
(This article belongs to the Special Issue Development of Novel Tumor-Targeting Nanoparticles)
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Review

Jump to: Research

22 pages, 1172 KiB  
Review
Novel Development of Nanoparticles—A Promising Direction for Precise Tumor Management
by Dengke Zhang, Qingqing Tang, Juan Chen, Yanghui Wei and Jiawei Chen
Pharmaceutics 2023, 15(1), 24; https://doi.org/10.3390/pharmaceutics15010024 - 21 Dec 2022
Cited by 5 | Viewed by 1964
Abstract
Although the clinical application of nanoparticles is still limited by biological barriers and distribution, with the deepening of our understanding of nanoparticles over the past decades, people are gradually breaking through the previous limitations in the diagnosis and treatment of tumors, providing novel [...] Read more.
Although the clinical application of nanoparticles is still limited by biological barriers and distribution, with the deepening of our understanding of nanoparticles over the past decades, people are gradually breaking through the previous limitations in the diagnosis and treatment of tumors, providing novel strategies for clinical decision makers. The transition of nanoparticles from passive targeting to active tumor-targeting by abundant surface-modified nanoparticles is also a development process of precision cancer treatment. Different particles can be used as targeted delivery tools of antitumor drugs. The mechanism of gold nanoparticles inducing apoptosis and cycle arrest of tumor cells has been discovered. Moreover, the unique photothermal effect of gold nanoparticles may be widely used in tumor therapy in the future, with less side effects on surrounding tissues. Lipid-based nanoparticles are expected to overcome the blood–brain barrier due to their special characteristics, while polymer-based nanoparticles show better biocompatibility and lower toxicity. In this paper, we discuss the development of nanoparticles in tumor therapy and the challenges that need to be addressed. Full article
(This article belongs to the Special Issue Development of Novel Tumor-Targeting Nanoparticles)
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30 pages, 4522 KiB  
Review
Polymeric Micelles for Breast Cancer Therapy: Recent Updates, Clinical Translation and Regulatory Considerations
by Vijayabhaskarreddy Junnuthula, Praveen Kolimi, Dinesh Nyavanandi, Sunitha Sampathi, Lalitkumar K. Vora and Sathish Dyawanapelly
Pharmaceutics 2022, 14(9), 1860; https://doi.org/10.3390/pharmaceutics14091860 - 3 Sep 2022
Cited by 45 | Viewed by 4106
Abstract
With the growing burden of cancer, parallel advancements in anticancer nanotechnological solutions have been witnessed. Among the different types of cancers, breast cancer accounts for approximately 25% and leads to 15% of deaths. Nanomedicine and its allied fields of material science have revolutionized [...] Read more.
With the growing burden of cancer, parallel advancements in anticancer nanotechnological solutions have been witnessed. Among the different types of cancers, breast cancer accounts for approximately 25% and leads to 15% of deaths. Nanomedicine and its allied fields of material science have revolutionized the science of medicine in the 21st century. Novel treatments have paved the way for improved drug delivery systems that have better efficacy and reduced adverse effects. A variety of nanoformulations using lipids, polymers, inorganic, and peptide-based nanomedicines with various functionalities are being synthesized. Thus, elaborate knowledge of these intelligent nanomedicines for highly promising drug delivery systems is of prime importance. Polymeric micelles (PMs) are generally easy to prepare with good solubilization properties; hence, they appear to be an attractive alternative over the other nanosystems. Although an overall perspective of PM systems has been presented in recent reviews, a brief discussion has been provided on PMs for breast cancer. This review provides a discussion of the state-of-the-art PMs together with the most recent advances in this field. Furthermore, special emphasis is placed on regulatory guidelines, clinical translation potential, and future aspects of the use of PMs in breast cancer treatment. The recent developments in micelle formulations look promising, with regulatory guidelines that are now more clearly defined; hence, we anticipate early clinical translation in the near future. Full article
(This article belongs to the Special Issue Development of Novel Tumor-Targeting Nanoparticles)
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32 pages, 1479 KiB  
Review
Multifunctional Nanoplatforms as a Novel Effective Approach in Photodynamic Therapy and Chemotherapy, to Overcome Multidrug Resistance in Cancer
by Martin Majerník, Rastislav Jendželovský, Jana Vargová, Zuzana Jendželovská and Peter Fedoročko
Pharmaceutics 2022, 14(5), 1075; https://doi.org/10.3390/pharmaceutics14051075 - 17 May 2022
Cited by 11 | Viewed by 2749
Abstract
It is more than sixty years since the era of modern photodynamic therapy (PDT) for cancer began. Enhanced selectivity for malignant cells with a reduced selectivity for non-malignant cells and good biocompatibility along with the limited occurrence of side effects are considered to [...] Read more.
It is more than sixty years since the era of modern photodynamic therapy (PDT) for cancer began. Enhanced selectivity for malignant cells with a reduced selectivity for non-malignant cells and good biocompatibility along with the limited occurrence of side effects are considered to be the most significant advantages of PDT in comparison with conventional therapeutic approaches, e.g., chemotherapy. The phenomenon of multidrug resistance, which is associated with drug efflux transporters, was originally identified in relation to the application of chemotherapy. Unfortunately, over the last thirty years, numerous papers have shown that many photosensitizers are the substrates of efflux transporters, significantly restricting the effectiveness of PDT. The concept of a dynamic nanoplatform offers a possible solution to minimize the multidrug resistance effect in cells affected by PDT. Indeed, recent findings have shown that the utilization of nanoparticles could significantly enhance the therapeutic efficacy of PDT. Additionally, multifunctional nanoplatforms could induce the synergistic effect of combined treatment regimens, such as PDT with chemotherapy. Moreover, the surface modifications that are associated with nanoparticle functionalization significantly improve the target potential of PDT or chemo-PDT in multidrug resistant and cancer stem cells. Full article
(This article belongs to the Special Issue Development of Novel Tumor-Targeting Nanoparticles)
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35 pages, 1771 KiB  
Review
The Landscape of Nanovectors for Modulation in Cancer Immunotherapy
by Simona-Ruxandra Volovat, Corina Lupascu Ursulescu, Liliana Gheorghe Moisii, Constantin Volovat, Diana Boboc, Dragos Scripcariu, Florin Amurariti, Cipriana Stefanescu, Cati Raluca Stolniceanu, Maricel Agop, Cristian Lungulescu and Cristian Constantin Volovat
Pharmaceutics 2022, 14(2), 397; https://doi.org/10.3390/pharmaceutics14020397 - 11 Feb 2022
Cited by 6 | Viewed by 2843
Abstract
Immunotherapy represents a promising strategy for the treatment of cancer, which functions via the reprogramming and activation of antitumor immunity. However, adverse events resulting from immunotherapy that are related to the low specificity of tumor cell-targeting represent a limitation of immunotherapy’s efficacy. The [...] Read more.
Immunotherapy represents a promising strategy for the treatment of cancer, which functions via the reprogramming and activation of antitumor immunity. However, adverse events resulting from immunotherapy that are related to the low specificity of tumor cell-targeting represent a limitation of immunotherapy’s efficacy. The potential of nanotechnologies is represented by the possibilities of immunotherapeutical agents being carried by nanoparticles with various material types, shapes, sizes, coated ligands, associated loading methods, hydrophilicities, elasticities, and biocompatibilities. In this review, the principal types of nanovectors (nanopharmaceutics and bioinspired nanoparticles) are summarized along with the shortcomings in nanoparticle delivery and the main factors that modulate efficacy (the EPR effect, protein coronas, and microbiota). The mechanisms by which nanovectors can target cancer cells, the tumor immune microenvironment (TIME), and the peripheral immune system are also presented. A possible mathematical model for the cellular communication mechanisms related to exosomes as nanocarriers is proposed. Full article
(This article belongs to the Special Issue Development of Novel Tumor-Targeting Nanoparticles)
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25 pages, 2613 KiB  
Review
Biomedical Applications of Iron Oxide Nanoparticles: Current Insights Progress and Perspectives
by María Gabriela Montiel Schneider, María Julia Martín, Jessica Otarola, Ekaterina Vakarelska, Vasil Simeonov, Verónica Lassalle and Miroslava Nedyalkova
Pharmaceutics 2022, 14(1), 204; https://doi.org/10.3390/pharmaceutics14010204 - 16 Jan 2022
Cited by 101 | Viewed by 7534
Abstract
The enormous development of nanomaterials technology and the immediate response of many areas of science, research, and practice to their possible application has led to the publication of thousands of scientific papers, books, and reports. This vast amount of information requires careful classification [...] Read more.
The enormous development of nanomaterials technology and the immediate response of many areas of science, research, and practice to their possible application has led to the publication of thousands of scientific papers, books, and reports. This vast amount of information requires careful classification and order, especially for specifically targeted practical needs. Therefore, the present review aims to summarize to some extent the role of iron oxide nanoparticles in biomedical research. Summarizing the fundamental properties of the magnetic iron oxide nanoparticles, the review’s next focus was to classify research studies related to applying these particles for cancer diagnostics and therapy (similar to photothermal therapy, hyperthermia), in nano theranostics, multimodal therapy. Special attention is paid to research studies dealing with the opportunities of combining different nanomaterials to achieve optimal systems for biomedical application. In this regard, original data about the synthesis and characterization of nanolipidic magnetic hybrid systems are included as an example. The last section of the review is dedicated to the capacities of magnetite-based magnetic nanoparticles for the management of oncological diseases. Full article
(This article belongs to the Special Issue Development of Novel Tumor-Targeting Nanoparticles)
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43 pages, 3693 KiB  
Review
Smart Lipid-Based Nanosystems for Therapeutic Immune Induction against Cancers: Perspectives and Outlooks
by Seth-Frerich Fobian, Ziyun Cheng and Timo L. M. ten Hagen
Pharmaceutics 2022, 14(1), 26; https://doi.org/10.3390/pharmaceutics14010026 - 23 Dec 2021
Cited by 17 | Viewed by 5729
Abstract
Cancer immunotherapy, a promising and widely applied mode of oncotherapy, makes use of immune stimulants and modulators to overcome the immune dysregulation present in cancer, and leverage the host’s immune capacity to eliminate tumors. Although some success has been seen in this field, [...] Read more.
Cancer immunotherapy, a promising and widely applied mode of oncotherapy, makes use of immune stimulants and modulators to overcome the immune dysregulation present in cancer, and leverage the host’s immune capacity to eliminate tumors. Although some success has been seen in this field, toxicity and weak immune induction remain challenges. Liposomal nanosystems, previously used as targeting agents, are increasingly functioning as immunotherapeutic vehicles, with potential for delivery of contents, immune induction, and synergistic drug packaging. These systems are tailorable, multifunctional, and smart. Liposomes may deliver various immune reagents including cytokines, specific T-cell receptors, antibody fragments, and immune checkpoint inhibitors, and also present a promising platform upon which personalized medicine approaches can be built, especially with preclinical and clinical potentials of liposomes often being frustrated by inter- and intrapatient variation. In this review, we show the potential of liposomes in cancer immunotherapy, as well as the methods for synthesis and in vivo progression thereof. Both preclinical and clinical studies are included to comprehensively illuminate prospects and challenges for future research and application. Full article
(This article belongs to the Special Issue Development of Novel Tumor-Targeting Nanoparticles)
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