The Laboratory of Clinical Pharmacy, The People's Hospital of Lishui, The Sixth Affiliated Hospital of Wenzhou Medical University, Lishui, China.
College of Pharmacy, Zhejiang Pharmaceutical College, Ningbo, China.
Drug Deliv Transl Res. 2022 Jan;12(1):167-179. doi: 10.1007/s13346-020-00895-1. Epub 2021 Jan 11.
Multidrug resistance (MDR) is considered as a critical limiting factor for the successful chemotherapy, which is mainly characterized by the overexpression of ATP-binding cassette (ABC) transporter ABCB1 or ABCG2. In this study, folate-targeted polymeric micellar carrier was successfully constructed to co-delivery of doxorubicin (DOX) and SIS3 (FA/DOX/SIS3 micelles), a specific Smad3 inhibitor which sensitizes ABCB1- and ABCG2-overexpressing cancer cells to chemotherapeutic agents. The ratio of DOX to SIS3 in polymeric micelles was determined based on the anti-tumor activity against resistant breast cells. In addition, FA/DOX/SIS3 micelles exhibited a much longer circulation time in blood and were preferentially accumulated in resistant tumor tissue. Pharmacodynamic studies showed that FA/DOX/SIS3 micelles possessed superior anti-tumor activity than other DOX-based treatments. Overall, FA/DOX/SIS3 micelles are a promising formulation for the synergistic treatment of drug-resistant tumor.
多药耐药性（MDR）被认为是化疗成功的关键限制因素，其主要特征是过度表达 ATP 结合盒（ABC）转运蛋白 ABCB1 或 ABCG2。在这项研究中，成功构建了叶酸靶向聚合物胶束载体来共递送阿霉素（DOX）和 SIS3（FA/DOX/SIS3 胶束），SIS3 是一种特异性 Smad3 抑制剂，可使过度表达 ABCB1 和 ABCG2 的癌细胞对化疗药物敏感。聚合物胶束中 DOX 与 SIS3 的比例是基于对耐药乳腺癌细胞的抗肿瘤活性来确定的。此外，FA/DOX/SIS3 胶束在血液中的循环时间更长，并优先聚集在耐药肿瘤组织中。药效学研究表明，FA/DOX/SIS3 胶束比其他基于 DOX 的治疗方法具有更好的抗肿瘤活性。总的来说，FA/DOX/SIS3 胶束是治疗耐药肿瘤的一种有前途的联合治疗制剂。
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