Fang Zhenhua, Sun Yanpeng, Xiao Hong, Li Peng, Liu Ming, Ding Fan, Kan Wusheng, Miao Runsheng
Department of Orthopaedics, Wuhan Puai Hospital, 473 Hanzheng Street, Wuhan, 430000, China.
Department of Orthopaedics, Luoyang Orthopedic-Traumatological Hospital, No. 1 Qiming Road, Luoyang, 450000, China.
Biomed Pharmacother. 2017 Jan;85:160-168. doi: 10.1016/j.biopha.2016.11.132. Epub 2016 Dec 5.
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 73nm depending on the DOX loading content. The release amount of DOX from RGD-DOX-PM achieved 63% within 60h under physiological condition. Interestingly, MTT assays in MG-63 and MNNG/HOS osteosarcoma cells exhibited that half-maximal inhibitory concentration (IC) 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.
骨肉瘤是儿童年龄组中最常见的原发性恶性骨肿瘤，由靶向纳米颗粒药物递送系统指导的化疗是近年来骨肉瘤治疗的一种有前景的方法。在此，我们设计并开发了一种新型的负载阿霉素的靶向聚合物胶束，它由RGD末端的聚（乙二醇）-嵌段-聚（碳酸三亚甲酯）（RGD-PEG-PTMC）两亲性可生物降解嵌段共聚物自组装而成，用于骨肉瘤的高效靶向化疗。值得注意的是，负载阿霉素的RGD修饰的可生物降解聚合物胶束（RGD-DOX-PM）的载药效率为57%-73%，根据阿霉素负载量的不同，其平均尺寸在46至73nm之间，分布较窄（PDI=0.05-0.12）。在生理条件下，RGD-DOX-PM中阿霉素的释放量在60小时内达到63%。有趣的是，在MG-63和MNNG/HOS骨肉瘤细胞中的MTT试验表明，RGD-DOX-PM的半数最大抑制浓度（IC）值远低于其非靶向对应物（DOX-PM），这意味着RGD修饰的纳米颗粒具有增强的细胞靶向能力，并导致更有效的抗肿瘤作用。此外，体外流式细胞术和共聚焦激光扫描显微镜（CLSM）成像试验证实了RGD-DOX-PM的靶向能力，结果显示MG-63细胞摄取的RGD-DOX-PM比DOX-PM更多。因此，这种RGD修饰的负载阿霉素的聚合物胶束在骨肉瘤的靶向化疗方面具有广阔前景。
