ROS-Activatable "off-on" Fluorescent Prodrug Loaded Micelles for Targeted Therapy and in Situ Imaging of Breast Cancer Cells.

This study developed an intelligent drug-loaded micelle system based on folic acid-conjugated polyglycidol (FAPG), which incorporates a reactive oxygen species (ROS) responsive fluorophore-drug conjugate (BTBP-PTX, BP). The system integrates folate receptor-α (FR-α) targeting, esterase/ROS dual-responsive drug release, and aggregation-induced emission (AIE)-based fluorescence activation for tumor-targeted delivery and imaging. Under simulated tumor microenvironment conditions (esterase-rich, high ROS levels), the system displayed dual-responsive release behavior, achieving over 80% paclitaxel (PTX) release within 24 h through esterase-catalyzed ester bond cleavage and ROS-triggered oxalate bond hydrolysis. Cellular assays demonstrated that BP@FAPG enhanced cellular uptake by approximately 2.5-fold in MDA-MB-231 cells compared to non-targeted controls BP@GAPG, along with significant cytotoxicity (IC50 = 60 nM) and deep penetration into three-dimensional tumor spheroids-effects primarily attributed to FR-α-mediated endocytosis. Furthermore, the AIE fluorophore was activated during drug release, allowing real-time fluorescence tracking of micelle localization and release dynamics.