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Enhanced Tumor Penetration and Chemotherapy Efficiency by Covalent Self-Assembled Nanomicelle Responsive to Tumor Microenvironment

The physicochemical properties of nanomedicine can be altered with a tumor microenvironment, which influence the precise delivery of drug molecules to the lesion. Thus, the therapeutic efficiency is restrained. Here, a covalent self-assembled nanomicelle (CSNM) based starburst polyprodrug was constr...

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Published in:Biomacromolecules 2019-07, Vol.20 (7), p.2637-2648
Main Authors: Ma, Xiaoqian, Bai, Shuang, Zhang, Xiaoli, Ma, Xianbin, Jia, Die, Shi, Xiaoxiao, Shao, Jinjun, Xue, Peng, Kang, Yuejun, Xu, Zhigang
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cited_by cdi_FETCH-LOGICAL-a342t-4ada49930b4bf4b6e33a39b7eaf45d191ee0a75e21866069b1e8eb1ace11eb4f3
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container_title Biomacromolecules
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creator Ma, Xiaoqian
Bai, Shuang
Zhang, Xiaoli
Ma, Xianbin
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Shao, Jinjun
Xue, Peng
Kang, Yuejun
Xu, Zhigang
description The physicochemical properties of nanomedicine can be altered with a tumor microenvironment, which influence the precise delivery of drug molecules to the lesion. Thus, the therapeutic efficiency is restrained. Here, a covalent self-assembled nanomicelle (CSNM) based starburst polyprodrug was constructed with the unimolecular micelle-templated self-assembly method and was expected to overcome biological barriers. It aimed to enhance the tumor penetration and chemotherapy efficiency of drugs. In CSNM, a hydrophilic copolymer was glued around a camptothecin (CPT) linked starburst polymeric prodrug [β-CD-P (CPT-co-NH2)] for protecting the positive charge of the prodrug with a reduction-triggered reversibility in conjugation and activity. Then, the complex was tracelessly delivered into a negatively charged cell membrane, leading to enhanced cellular uptake. Finally, the disulfide bond in the CPT prodrug can be broken under the reductive microenvironment within tumor cells and liberated the CPT molecules. Both in vitro and in vivo results demonstrated the benefits of our CSNM system, including high drug loading, controllable drug release, excellent uptake by tumor cells and remarkable antitumor efficiency. In essence, our findings suggested CSNM as an innovative strategy for drug delivery in chemotherapy, producing a competitive versatility in the development of biomedicine.
doi_str_mv 10.1021/acs.biomac.9b00424
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title Enhanced Tumor Penetration and Chemotherapy Efficiency by Covalent Self-Assembled Nanomicelle Responsive to Tumor Microenvironment
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