Reductive microenvironment-activated paclitaxel-BODIPY nanoassemblies for self-reporting drug delivery.
We report the design and synthesis of a redox-responsive paclitaxel-BODIPY conjugate (PTX-SS-BDP) in which paclitaxel is linked to a BODIPY moiety through a glutathione-cleavable disulfide spacer. The amphiphilic conjugate readily self-assembles into PEGylated nanoparticles with excellent colloidal stability and efficient cellular uptake. Under intracellular reducing conditions, cleavage of the disulfide linker triggers the simultaneous release of paclitaxel and fluorescence ON response for the BODIPY reporter moiety, enabling real-time monitoring of prodrug activation. The nanoparticles exhibit glutathione-dependent drug release kinetics and preferential activation in MCF-7 breast cancer cells over normal MCF-10A mammary epithelial cells. Consequently, PTX-SS-BDP nanoparticles display enhanced cytotoxicity toward MCF-7 cells compared with free paclitaxel, while maintaining reduced toxicity toward MCF-10A cells. This study demonstrates a simple molecular strategy for constructing self-assembling fluorogenic prodrugs that integrate redox-responsive chemotherapy with fluorescence-guided monitoring.