胶束
阿霉素
化学
透明质酸
CD44细胞
药物输送
癌症研究
生物相容性
肿瘤微环境
化疗
生物物理学
细胞
生物化学
医学
肿瘤细胞
生物
有机化学
水溶液
外科
解剖
作者
Panpan Song,Zhongxia Lu,Tianze Jiang,Wenwei Han,Xiangyan Chen,Xia Zhao
标识
DOI:10.1016/j.ijbiomac.2022.09.245
摘要
The complex tumor microenvironment (TME) makes it difficult for single chemotherapy to achieve satisfactory therapeutic effects. Here, chitosan-coated hyaluronic acid micelles (R/C/D@HAssOA) that co-delivers doxorubicin (DOX) and programmed death-ligand 1 small interfering RNA (siPD-L1) are developed to enhance anti-tumor effect by combination of immunotherapy and chemotherapy. The pH/reduction dual-responsive co-delivery micelles R/C/D@HAssOA are spherical particles about 180 nm, and have good drug loading performance, stability, biocompatibility, and TME-responsive drug release properties. The CD44 receptor targeting HA significantly enhances the cellular uptake of DOX and siPD-L1, and siPD-L1 causes the immune infiltration of CD4+/CD8+ T cells by silencing PD-L1 expression. In vivo studies show that R/C/D@HAssOA exhibits significantly stronger anti-breast cancer effect than that of free DOX and micelles loaded only DOX. Therefore, the dual-stimulus responsive micelles provide a promising strategy for combining chemotherapy and siRNA-based immunotherapy to enhance efficacy.
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