Engineering endoplasmic reticulum targeted metal-polyphenol curcumin nanomicelles for melanoma therapy.

ABSTRACT: Melanoma has a high incidence and mortality, and current therapies are limited. Here, we developed TCPC, an ER-targeted nanomedicine guided by omics analysis. It consists of curcumin-loaded PEG-PCL nanomicelles coated with a Tannic acid-Cu metal-polyphenol network. Guided by clinical transcriptome mining, we identified ER-stress vulnerabilities to inform material design. RNA-seq and imaging confirmed that TCPC preferentially accumulates in melanoma cells and localizes to the ER. TCPC markedly elevates CHOP expression, which triggers ER Ca²⁺ release, mitochondrial dysfunction, ROS accumulation, and apoptosis. Functionally, TCPC significantly suppresses cell viability, migration, and invasion in vitro. In melanoma xenografts, systemic TCPC treatment slows tumor growth, enhances intratumoral

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC12859999 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature