Copper-coordination driven brain-targeting nanoassembly for efficient glioblastoma multiforme immunotherapy by cuproptosis-mediated tumor immune microenvironment reprogramming.

ABSTRACT: Limited drug accumulation and an immunosuppressive microenvironment are the major bottlenecks in the treatment of glioblastoma multiforme (GBM). Herein, we report a copper-coordination driven brain-targeting nanoassembly (TCe6@Cu/TP5 NPs) for site-specific delivery of therapeutic agents and efficient immunotherapy by activating the cGAS-STING pathway and downregulating the expression of PD-L1. To achieve this, the mitochondria-targeting triphenylphosphorus (TPP) was linked to photosensitizer Chlorin e6 (Ce6) to form TPP-Ce6 (TCe6), which was then self-assembled with copper ions and thymopentin (TP5) to obtain TCe6@Cu/TP5 NPs. This nanoassembly effectively accumulated in tumor sites through the copper transport mechanism. Meanwhile, TCe6@Cu/TP5 could induce mitochondrial impairment by photo

SUBMITTER: Chen Y 

PROVIDER: S-EPMC11681643 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature