Tumor microenvironment-responsive PEGylated heparin-pyropheophorbide-a nanoconjugates for photodynamic therapy.
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.
['Wu|Yahui|Y|', 'Li|Fangnian|F|', 'Zhang|Xiaoqin|X|', 'Li|Zhiqian|Z|', 'Zhang|Qianfeng|Q|', 'Wang|Wenjia|W|', 'Pan|Dayi|D|', 'Zheng|Xiuli|X|', 'Gu|Zhongwei|Z|', 'Zhang|Hu|H|', 'Gong|Qiyong|Q|', 'Luo|Kui|K|']
D000818:Animals D000970:Antineoplastic Agents D017209:Apoptosis D045744:Cell Line, Tumor D002470:Cell Survival D002734:Chlorophyll D005260:Female D006493:Heparin D007834:Lasers D008027:Light D008325:Mammary Neoplasms, Experimental D051379:Mice D008807:Mice, Inbred BALB C D058726:Nanoconjugates D010778:Photochemotherapy D017319:Photosensitizing Agents D011092:Polyethylene Glycols D017382:Reactive Oxygen Species D018874:Spheroids, Cellular D016896:Treatment Outcome D047368:Tumor Burden D059016:Tumor Microenvironment
PEGylation Photodynamic therapy Heparin Nanomedicines Tumor microenvironment