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Development of Mitomycin C-Loaded Nanoparticles Prepared Using the Micellar Assembly Driven by the Combined Effect of Hydrogen Bonding and π–π Stacking and Its Therapeutic Application in Bladder Cancer
Micelle is mainly used for drug delivery and is prepared from amphiphilic block copolymers. It can be formed into an obvious core-shell structure that can incorporate liposoluble drugs. However, micelles are not suitable for the encapsulation of water-soluble drugs, and it is also difficult to maint...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8624376/ https://www.ncbi.nlm.nih.gov/pubmed/34834192 http://dx.doi.org/10.3390/pharmaceutics13111776 |
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author | Qi, Lingling Liu, Chao Zhang, Yingying Zhang, Zheao Duan, Hongxia Zhao, Heming Xin, Xin Chen, Liqing Jin, Mingji Guan, Youyan Gao, Zhonggao Huang, Wei |
author_facet | Qi, Lingling Liu, Chao Zhang, Yingying Zhang, Zheao Duan, Hongxia Zhao, Heming Xin, Xin Chen, Liqing Jin, Mingji Guan, Youyan Gao, Zhonggao Huang, Wei |
author_sort | Qi, Lingling |
collection | PubMed |
description | Micelle is mainly used for drug delivery and is prepared from amphiphilic block copolymers. It can be formed into an obvious core-shell structure that can incorporate liposoluble drugs. However, micelles are not suitable for the encapsulation of water-soluble drugs, and it is also difficult to maintain stability in the systemic circulation. To solve these problems, a type of polymer material, Fmoc-Lys-PEG and Fmoc-Lys-PEG-RGD, was designed and synthesized. These copolymers could self-assemble into micelles driven by π–π stacking and the hydrophobic interaction of 9-fluorenylmethoxycarbony (Fmoc) and, at the same time, form a framework for a hydrogen-bonding environment in the core. Mitomycin C (MMC), as a water-soluble drug, can be encapsulated into micelles by hydrogen-bonding interactions. The interaction force between MMC and the polymers was analyzed by molecular docking simulation and Fourier transform infrared (FTIR). It was concluded that the optimal binding conformation can be obtained, and that the main force between the MMC and polymers is hydrogen bonding. Different types of MMC nanoparticles (NPs) were prepared and the physicochemical properties of them were systematically evaluated. The pharmacodynamics of the MMC NPs in vitro and in vivo were also studied. The results show that MMC NPs had a high uptake efficiency, could promote cell apoptosis, and had a strong inhibitory effect on cell proliferation. More importantly, the as-prepared NPs could effectively induce tumor cell apoptosis and inhibit tumor growth and metastasis in vivo. |
format | Online Article Text |
id | pubmed-8624376 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-86243762021-11-27 Development of Mitomycin C-Loaded Nanoparticles Prepared Using the Micellar Assembly Driven by the Combined Effect of Hydrogen Bonding and π–π Stacking and Its Therapeutic Application in Bladder Cancer Qi, Lingling Liu, Chao Zhang, Yingying Zhang, Zheao Duan, Hongxia Zhao, Heming Xin, Xin Chen, Liqing Jin, Mingji Guan, Youyan Gao, Zhonggao Huang, Wei Pharmaceutics Article Micelle is mainly used for drug delivery and is prepared from amphiphilic block copolymers. It can be formed into an obvious core-shell structure that can incorporate liposoluble drugs. However, micelles are not suitable for the encapsulation of water-soluble drugs, and it is also difficult to maintain stability in the systemic circulation. To solve these problems, a type of polymer material, Fmoc-Lys-PEG and Fmoc-Lys-PEG-RGD, was designed and synthesized. These copolymers could self-assemble into micelles driven by π–π stacking and the hydrophobic interaction of 9-fluorenylmethoxycarbony (Fmoc) and, at the same time, form a framework for a hydrogen-bonding environment in the core. Mitomycin C (MMC), as a water-soluble drug, can be encapsulated into micelles by hydrogen-bonding interactions. The interaction force between MMC and the polymers was analyzed by molecular docking simulation and Fourier transform infrared (FTIR). It was concluded that the optimal binding conformation can be obtained, and that the main force between the MMC and polymers is hydrogen bonding. Different types of MMC nanoparticles (NPs) were prepared and the physicochemical properties of them were systematically evaluated. The pharmacodynamics of the MMC NPs in vitro and in vivo were also studied. The results show that MMC NPs had a high uptake efficiency, could promote cell apoptosis, and had a strong inhibitory effect on cell proliferation. More importantly, the as-prepared NPs could effectively induce tumor cell apoptosis and inhibit tumor growth and metastasis in vivo. MDPI 2021-10-25 /pmc/articles/PMC8624376/ /pubmed/34834192 http://dx.doi.org/10.3390/pharmaceutics13111776 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Qi, Lingling Liu, Chao Zhang, Yingying Zhang, Zheao Duan, Hongxia Zhao, Heming Xin, Xin Chen, Liqing Jin, Mingji Guan, Youyan Gao, Zhonggao Huang, Wei Development of Mitomycin C-Loaded Nanoparticles Prepared Using the Micellar Assembly Driven by the Combined Effect of Hydrogen Bonding and π–π Stacking and Its Therapeutic Application in Bladder Cancer |
title | Development of Mitomycin C-Loaded Nanoparticles Prepared Using the Micellar Assembly Driven by the Combined Effect of Hydrogen Bonding and π–π Stacking and Its Therapeutic Application in Bladder Cancer |
title_full | Development of Mitomycin C-Loaded Nanoparticles Prepared Using the Micellar Assembly Driven by the Combined Effect of Hydrogen Bonding and π–π Stacking and Its Therapeutic Application in Bladder Cancer |
title_fullStr | Development of Mitomycin C-Loaded Nanoparticles Prepared Using the Micellar Assembly Driven by the Combined Effect of Hydrogen Bonding and π–π Stacking and Its Therapeutic Application in Bladder Cancer |
title_full_unstemmed | Development of Mitomycin C-Loaded Nanoparticles Prepared Using the Micellar Assembly Driven by the Combined Effect of Hydrogen Bonding and π–π Stacking and Its Therapeutic Application in Bladder Cancer |
title_short | Development of Mitomycin C-Loaded Nanoparticles Prepared Using the Micellar Assembly Driven by the Combined Effect of Hydrogen Bonding and π–π Stacking and Its Therapeutic Application in Bladder Cancer |
title_sort | development of mitomycin c-loaded nanoparticles prepared using the micellar assembly driven by the combined effect of hydrogen bonding and π–π stacking and its therapeutic application in bladder cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8624376/ https://www.ncbi.nlm.nih.gov/pubmed/34834192 http://dx.doi.org/10.3390/pharmaceutics13111776 |
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