Tumor microenvironment-responsive conformational activation of apoA-I mimetic peptides for targeted cancer therapy.

ABSTRACT: Apolipoprotein A-I (ApoA-I) mimetic peptides have garnered attention as potential anticancer agents owing to their role in cholesterol metabolism and ability to interact with the SR-BI receptor. However, their tendency to form lipid-bound structures in circulation limits their tumor-targeting therapeutic potential and raises the risk of off-target effects. In this study, we engineered a stimuli-responsive ApoA-I mimetic peptide by incorporating reactive oxygen species (ROS) -responsive amino acid derivatives into its sequence. Under normal physiological conditions, the peptide adopted a disordered conformation, minimizing nonspecific interactions. In contrast, the exposure to the tumor microenvironment, which is characterized by low pH and elevated ROS, could trigger a conformational trans

SUBMITTER: Rui M 

PROVIDER: S-EPMC12713209 | biostudies-literature | 2026 Dec

REPOSITORIES: biostudies-literature