Interleukin-15 and cisplatin co-encapsulated thermosensitive polypeptide hydrogels for combined immuno-chemotherapy
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 3 weeks 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.Graphical abstract
The mechanism for synergistic antitumor effects of coadministration of IL-15 and CDDP released from the mPEG-b-PELG hydrogels.