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

作　　者：Qiang Lv Chaoliang He Fenli Quan Shuangjiang Yu Xuesi Chen 

机构地区：[1]Institute of Translational Medicine,The First Hospital of Jilin University,Changchun,130021,China [2]Key Laboratory of Polymer Ecomaterials,Changchun Institute of Applied Chemistry,Chinese Academy of Sciences,Changchun,130022,China

出　　处：《Bioactive Materials》2018年第1期118-128,共11页生物活性材料（英文）

基　　金：The financial support from the National Natural Science Foundation of China(No.51403202,51622307,51390484,51520105004)are gratefully thanked.

摘　　要：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.

关 键 词：Polypeptide hydrogel Sustained co-delivery Combination therapy Local cancer treatment Thermosensitive hydrogel 

分 类 号：R73[医药卫生—肿瘤]