DOX/IL-2/IFN-g co-loaded thermo-sensitive polypeptide hydrogel for efficient melanoma treatment

Melanoma has been a serious threat to the human health;however,effective therapeutic methods of this cancer are still limited.Combined local therapy is a crucial approach for achieving a superior anti-tumor efficacy.In this paper,a chemo-immunotherapy system of DOX,IL-2 and IFN-g based on poly(g-ethyl-Lglutamate)-poly(ethylene glycol)-poly(g-ethyl-L-glutamate)(PELG-PEG-PELG)hydrogel was developed for local treatment of melanoma xenograft.The drug release process of this system exhibited a short term of burst release(the first 3 days),followed by a long-term sustained release(the following 26 days).The hydrogel degraded completely within 3 weeks without obvious inflammatory responses in the subcutaneous layer of rats,showing a good biodegradability and biocompatibility.The DOX/IL-2/IFN-g co-loaded hydrogel also showed enhanced anti-tumor effect against B16F10 cells in vitro,through increasing the ratio of cell apoptosis and G2/S phage cycle arrest.Moreover,the combined strategy presented improved therapy efficacy against B16F10 melanoma xenograft without obvious systemic side effects in a nude mice model,which was likely related to both the enhanced tumor cell apoptosis and the increased proliferation of the CD3t/CD4t T-lymphocytes and CD3t/CD8t T-lymphocytes.Overall,the strategy of localized co-delivery of DOX/IL-2/IFN-g using the polypeptide hydrogel provided a promising approach for efficient melanoma therapy.