期刊
CARBOHYDRATE POLYMERS
卷 255, 期 -, 页码 -出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.carbpol.2020.117490
关键词
Heparin; PEGylation; Tumor microenvironment; Photodynamic therapy; Nanomedicines
资金
- National Natural Science Foundation of China [51873120, 51673127, 81621003]
- Department of Science and Technology of Sichuan Province [2018JY0574]
- PostDoctor Research Project, West China Hospital, Sichuan University [2018HXBH055]
PEGylated heparin-based nanomedicines prepared in this study showed significant anticancer efficacy in vivo for photodynamic therapy. By modulating the conjugation of PEG moieties, the penetration and anticancer effects of the nanoparticles on tumor tissues were successfully enhanced.
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.
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