Department of Drug Discovery and Biomedical Sciences, University of South Carolina, 715 Sumter St., Columbia, SC 29208, USA.
Department of Biological Sciences, University of South Carolina, 715 Sumter St., Columbia, SC 29208, USA.
Biomater Sci. 2023 Aug 8;11(16):5641-5652. doi: 10.1039/d3bm00627a.
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 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.
我们之前的研究发现，将 PDA-PEG 聚合物与铜离子结合可以选择性地杀死癌细胞。然而，这种结合的精确机制尚不完全清楚。本研究表明，PDA-PEG 聚合物和铜离子通过促进铜离子摄取和溶酶体逃逸，形成互补的 PDA-PEG/铜（Poly/Cu）纳米复合物。一项研究发现，Poly/Cu 通过溶酶体细胞死亡途径杀死 4T1 细胞。此外，Poly/Cu 抑制蛋白酶体功能和自噬途径，并在 4T1 细胞中诱导免疫原性细胞死亡（ICD）。Poly/Cu 诱导的 ICD 与抗 PD-L1 抗体（aPD-L1）的检查点阻断效应协同作用，促进免疫细胞渗透到肿瘤组织中。得益于 Poly/Cu 复合物的肿瘤靶向和癌细胞选择性杀伤作用，aPD-L1 和 Poly/Cu 的联合治疗有效地抑制了三阴性乳腺癌的进展，而没有引起全身副作用。
