Cystine proportion regulates fate of polypeptide nanogel as nanocarrier for chemotherapeutics

• 作者: Xiangru Feng Weiguo Xu Xiaoru Xu Gao Li Jianxun Ding Xuesi Chen
• 来源期刊: 中国科学：化学（英文版）
• 年，卷（期）: 2021,（2）
• 所属期刊栏目: ARTICLES
• 页码范围: 293-301
• 页数: 9页
• 语种: 英文

摘要

The physicochemical characteristics of nanoparticles are closely related to their drug delivery performances in vitro and in vivo.A well-designed nanocarrier can prolong the drug half-life in the blood circulation,upregulate the drug accumulation at the target site,and enhance the treatment efficacy.To elucidate the impact of physicochemical properties on the fate of nanogel as a nanocarrier of chemotherapeutics,three methoxy poly(ethylene glycol)-poly(L-phenylalanine-co-L-cystine)(mPEG-P(LP-co-LC))nanogels with different L-cystine proportions were developed,namely mPEG-P(LP10-co-LC5)(NG10-5),mPEG-P(LP10-co-LC10)(NG10-10),and mPEG-P(LP10-co-LC15)(NG10-15).The three nanogels shared similar surface charge and reduction-responsive behavior,but they had distinct diameters and different drug release profiles.Among them,NG10-5,which has the smallest diameter,was preferentially internalized by tumor cells in vitro and showed rapid migration to the tumor site in vivo.Using doxorubicin(DOX)as a model chemotherapeutic agent,NG10-5/DOX had the most prolonged blood circulation period and highest tumor accumulation after intravenous administration.NG10-5/DOX also had the most potent antitumor effect of all three drug-loaded nanogels.Accordingly,adjusting physicochemical characteristics by changing the amino acid composition might improve the therapeutic effiicacies of nanogels and enhance their potential for clinical application.