Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, People's Republic of China; University of Chinese Academy of Sciences, Beijing 100039, People's Republic of China.
Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, People's Republic of China.
J Control Release. 2017 Jun 10;255:81-93. doi: 10.1016/j.jconrel.2017.04.011. Epub 2017 Apr 10.
In situ-forming thermosensitive hydrogels based on poly(ethylene glycol)-poly(γ-ethyl-l-glutamate) diblock copolymers (mPEG-b-PELG) were prepared for the co-delivery of interleukin-15 (IL-15) and cisplatin (CDDP). The polypeptide-based hydrogels as local drug delivery carriers could reduce the systemic toxicity, degrade thoroughly within 3weeks after subcutaneous injection into rats and display an acceptable biocompatibility. When incubated with mouse melanoma B16 cells, only the CDDP-treated groups had significant effects on the S phase cell-cycle arrest in melanoma cells. After a single peritumoral injection of the hydrogel containing IL-15/CDDP in C57BL/6 mice inoculated with B16F0-RFP melanoma cells, the dual drug-loaded hydrogels displayed synergistic anticancer efficacy, which was resulted from a combination of CDDP-mediated S arrest and IL-15/CDDP-induced recovery of CD8 T cell and NK cell populations to reduce immunosuppression and enhance antitumor immunity. Hence, the as-prepared thermosensitive polypeptide hydrogels for localized and sustained co-delivery of IL-15 and CDDP may have potential for efficient treatment of melanoma.
基于聚乙二醇-聚（γ-乙基-L-谷氨酸）两亲嵌段共聚物（mPEG-b-PELG）的原位形成温敏水凝胶被制备用于白细胞介素 15（IL-15）和顺铂（CDDP）的共递送。作为局部药物递送载体的多肽水凝胶可以降低全身毒性，在皮下注射到大鼠体内 3 周内完全降解，并具有可接受的生物相容性。当与小鼠黑色素瘤 B16 细胞孵育时，只有 CDDP 处理组对黑色素瘤细胞的 S 期细胞周期阻滞有显著影响。在 C57BL/6 小鼠皮下注射含有 IL-15/CDDP 的水凝胶后，B16F0-RFP 黑色素瘤细胞接种后，双载药水凝胶显示出协同的抗癌疗效，这是由于 CDDP 介导的 S 期阻滞和 IL-15/CDDP 诱导的 CD8 T 细胞和 NK 细胞群恢复相结合，从而减少免疫抑制并增强抗肿瘤免疫。因此，用于局部和持续共递送 IL-15 和 CDDP 的这种温敏多肽水凝胶可能具有有效治疗黑色素瘤的潜力。
