A cell membrane-targeted AIEgen nanoparticle synergistically enhances cisplatin chemotherapy via localized photodynamic therapy

As a conventional cancer therapy, chemotherapy often causes serious side effects when used at therapeutic doses. To address these limitations, we employ a photosensitizer named DTTPB from our previous study for cell membrane-targeted photodynamic therapy (PDT) to boost chemotherapy efficacy. This AIEgen features a unique amphiphilic D–π–A architecture that enables precise plasma membrane anchoring. Unlike conventional dual-drug co-loaded nanosystems, our single-component DTTPB@PEG platform greatly simplifies the formulation. DTTPB demonstrates remarkable stability and biocompatibility both in dark and under light irradiation. It anchors onto the cell membrane and generates ROS upon light exposure, inducing cell membrane lipid peroxidation and thereby effectively enhancing cisplatin uptake and cytotoxicity under light irradiation. Besides, DTTPB@PEG could accumulate at the tumor sites, facilitating enhanced CDDP uptake and pathological changes in major organs. This combination therapy offers a promising strategy for enhancing the efficacy of chemotherapy while reducing systemic toxicity, highlighting its potential for clinical translation.