Targeted osteosarcoma chemotherapy using RGD peptide-installed doxorubicin-loaded biodegradable polymeric micelle

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• 作者：Zhenhua Fang^a ; ¹ ; Yanpeng Sun^b ; ¹ ; Hong Xiao^a ; Peng Li^a ; Ming Liu^a ; Fan Ding^a ; Wusheng Kan^a ; Runsheng Miao^a ; ^{strongspine@163.com}
• 关键词：Osteosarcoma ; Targeted chemotherapy ; Nanoparticulate drug delivery system ; RGD
• 刊名：Biomedicine & Pharmacotherapy
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：85
• 期：Complete
• 页码：160-168
• 全文大小：1862 K
• 卷排序：85

文摘

Osteosarcoma is the most common primary malignant bone tumor in the pediatric age group, and chemotherapy directed by targeted nanoparticulate drug delivery system represents a promising approach for osteosarcoma treatment recently. Here, we designed and developed a novel DOX-loaded targeted polymeric micelle self-assembled from RGD-terminated poly(ethylene glycol)-block-poly (trimethylene carbonate) (RGD-PEG-PTMC) amphiphilic biodegradable block copolymer, for high-efficiency targeted chemotherapy of osteosarcoma. Notably, the RGD-installed DOX-loaded biodegradable polymeric micelle (RGD-DOX-PM) with drug loading efficiency of 57%–73% displayed a narrow distribution (PDI = 0.05–0.12) with average sizes ranging from 46 to 73 nm depending on the DOX loading content. The release amount of DOX from RGD-DOX-PM achieved 63% within 60 h under physiological condition. Interestingly, MTT assays in MG-63 and MNNG/HOS osteosarcoma cells exhibited that half-maximal inhibitory concentration (IC50) value of RGD-DOX-PM was much lower than its non-targeted counterpart (DOX-PM), implying RGD decorated nanoparticles had enhanced cell targeting ability and led to more effective anti-tumor effect. Furthermore, the targeting ability of RGD-DOX-PM was confirmed by in vitro flow cytometry and confocal laser scanning microscopy (CLSM) imaging assays, where the results showed more RGD-DOX-PM were taken up by MG-63 cells than that of DOX-PM. Therefore, this RGD decorated DOX-loaded polymeric micelle is promising for targeted chemotherapy of osteosarcoma.