自噬
溶酶体
程序性细胞死亡
化学
癌症研究
癌细胞
免疫原性细胞死亡
肿瘤微环境
免疫疗法
三阴性乳腺癌
癌症免疫疗法
体外
细胞
免疫系统
生物物理学
乳腺癌
癌症
免疫学
生物
生物化学
医学
细胞凋亡
肿瘤细胞
内科学
酶
作者
Xinran Hu,Mingming Wang,Shanshan Shi,Manikanda Raja Keerthi Raja,Gourab Sen Gupta,Hexin Chen,Pao Xu
出处
期刊:Biomaterials Science
[The Royal Society of Chemistry]
日期:2023-01-01
卷期号:11 (16): 5641-5652
摘要
Our previous research discovered that combining the PDA-PEG polymer with copper ions can selectively kill cancer cells. However, the precise mechanism by which this combination functions was not fully understood. This study revealed that the PDA-PEG polymer and copper ions form complementary PDA-PEG/copper (Poly/Cu) nanocomplexes by facilitating copper ion uptake and lysosomal escape. An in vitro study found that Poly/Cu killed 4T1 cells through a lysosome cell death pathway. Furthermore, Poly/Cu inhibited both the proteasome function and autophagy pathway and induced immunogenic cell death (ICD) in 4T1 cells. The Poly/Cu induced ICD coupled with the checkpoint blockade effect of the anti-PD-L1 antibody (aPD-L1) synergistically promoted immune cell penetration into the tumor mass. Benefiting from the tumor-targeting effect and cancer cell-selective killing effect of Poly/Cu complexes, the combinatory treatment of aPD-L1 and Poly/Cu effectively suppressed the progression of triple-negative breast cancer without inducing systemic side effects.
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