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Tumor microenvironment-responsive PEGylated heparin-pyropheophorbide-a nanoconjugates for photodynamic therapy.

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机构： [1]Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital, Functional and Molecular Imaging Key Laboratory of Sichuan Province, SichuanUniversity, Chengdu, 610041, China [2]Research Unit of Psychoradiology, Chinese Academy of Medical Sciences, Chengdu, 610041, China [3]College of Preclinical Medicine, Southwest Medical University, Luzhou, 646000, China [4]Amgen Bioprocessing Centre, Keck Graduate Institute, CA, 91711, USA [5]Kindos Pharmaceutical Co., Ltd., No. 8-9 Kexin Road, Chengdu Hi-Tech Comprehensive Bonded Zone, Chengdu, 611731, China

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关键词： Heparin PEGylation Tumor microenvironment Photodynamic therapy Nanomedicines

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To deliver photosensitizers with PEGylated heparin (HP) into tumor cells for photodynamic therapy, we prepared two polyethylene glycol (PEG)-functionalized HP-based polymers conjugated with pyropheophorbide-a (Ppa): a non-GSH-responsive nanoagent (HP-Ppa-mPEG) with the mPEG moiety chemically attached to HP directly; and a GSH-responsive nanoagent (HP-Ppa-SS-mPEG) with the mPEG moiety conjugated to HP via a disulfide linkage. The Ppa-functionalized HP without PEGylation (HP-Ppa) was designed as another control. These amphiphilic polymers could aggregate into nanoparticles. Cellular uptake of three nanoparticles by 4T1 cells led to abundant production of reactive oxygen species after irradiation by a 660 nm laser, inducing cell apoptosis. HP-Ppa-SS-mPEG was found to achieve the highest tumor accumulation, the longest retention time and the best penetration into tumor tissues, resulting in the highest in vivo anticancer efficacy with 94.3 % tumor growth inhibition rate, suggesting that tumor microenvironment-responsive PEGylated HP-based nanomedicines may act as efficient anticancer agents. Copyright © 2020 Elsevier Ltd. All rights reserved.

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出版当年[2021]版：

大类 | 1 区

化学

小类 | 1 区应用化学 1 区有机化学 1 区高分子科学

最新[2023]版：

大类 | 1 区

化学

小类 | 1 区应用化学 1 区有机化学 1 区高分子科学

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第一作者机构： [1]Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital, Functional and Molecular Imaging Key Laboratory of Sichuan Province, SichuanUniversity, Chengdu, 610041, China

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