期刊
BIOACTIVE MATERIALS
卷 3, 期 1, 页码 118-128出版社
KEAI PUBLISHING LTD
DOI: 10.1016/j.bioactmat.2017.08.003
关键词
Polypeptide hydrogel; Sustained co-delivery; Combination therapy; Local cancer treatment; Thermosensitive hydrogel
资金
- National Natural Science Foundation of China [51403202, 51622307, 51390484, 51520105004]
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-gamma based on poly(gamma-ethyl-L-glutamate)-poly(ethylene glycol)-poly(gamma-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-gamma 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 CD3(+)/CD4(+) T-lymphocytes and CD3(+)/CD8(+) T-lymphocytes. Overall, the strategy of localized co-delivery of DOX/IL-2/IFN-gamma using the polypeptide hydrogel provided a promising approach for efficient melanoma therapy. (c) 2017 The Authors. Production and hosting by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.
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