Soe Zar Chi, Kwon Jun Bum, Thapa Raj Kumar, Ou Wenquan, Nguyen Hanh Thuy, Gautam Milan, Oh Kyung Taek, Choi Han-Gon, Ku Sae Kwang, Yong Chul Soon, Kim Jong Oh
College of Pharmacy, Yeungnam University, 214-1, Dae-dong, Gyeongsan 712-749, Korea.
Department of Pharmaceutics, University of Pharmacy (Yangon), Waybargi Road, North Okkalapa township, Yangon 11031, Myanmar.
Pharmaceutics. 2019 Feb 1;11(2):63. doi: 10.3390/pharmaceutics11020063.
In this study, a transferrin (T)-conjugated polymeric nanoparticle was developed for the targeted delivery of the chemotherapeutic agent doxorubicin (Dox) in order to overcome multi-drug resistance in cancer treatment. Our objective was to improve Dox delivery for producing significant antitumor efficacy in Dox-resistant (R) breast cancer cell lines with minimum toxicity to healthy cells. The results of our experiments revealed that Dox was successfully loaded inside a transferrin (T)-conjugated polymeric nanoparticle composed of poloxamer 407 (F127) and 123 (P123) (Dox/F127P123-T), which produced nanosized particles (90 nm) with a low polydispersity index (0.23). The accelerated and controlled release profiles of Dox from the nanoparticles were characterized in acidic and physiological pH and Dox/F127P123-T enhanced Dox cytotoxicity in OVCAR-3, MDA-MB-231, and MDA-MB-231(R) cell lines through induction of cellular apoptosis. Moreover, Dox/F127P123-T inhibited cell migration and altered the cell cycle patterns of different cancer cells. In vivo study in MDA-MB-231(R) tumor-bearing mice demonstrated enhanced delivery of nanoparticles to the tumor site when coated in a targeting moiety. Therefore, Dox/F127P123-T has been tailored, using the principles of nanotherapeutics, to overcome drug-resistant chemotherapy.
在本研究中，开发了一种转铁蛋白（T）共轭聚合物纳米颗粒，用于化疗药物阿霉素（Dox）的靶向递送，以克服癌症治疗中的多药耐药性。我们的目标是改善阿霉素的递送，以便在对阿霉素耐药（R）的乳腺癌细胞系中产生显著的抗肿瘤功效，同时对健康细胞的毒性最小。我们的实验结果表明，阿霉素成功负载于由泊洛沙姆407（F127）和123（P123）组成的转铁蛋白（T）共轭聚合物纳米颗粒中（Dox/F127P123-T），该纳米颗粒产生了低多分散指数（约0.23）的纳米级颗粒（约90 nm）。在酸性和生理pH条件下对纳米颗粒中阿霉素的加速和控释特性进行了表征，并且Dox/F127P123-T通过诱导细胞凋亡增强了对卵巢癌3（OVCAR-3）、人乳腺癌细胞系（MDA-MB-231）和耐阿霉素人乳腺癌细胞系（MDA-MB-231(R)）的细胞毒性。此外，Dox/F127P123-T抑制细胞迁移并改变不同癌细胞的细胞周期模式。在携带MDA-MB-231(R)肿瘤的小鼠体内研究表明，当包裹在靶向部分时，纳米颗粒向肿瘤部位的递送增强。因此，利用纳米治疗学原理定制了Dox/F127P123-T，以克服耐药化疗。
