Safer photodynamic therapy with nanomicelles of heavy atom-free triazine-BODIPY hybrids

In this study, a series of novel triazine-BODIPY derivatives bearing varying numbers of orthogonal BODIPY units and hydrophilic triethylene glycol substituents, and their water-soluble nanomicelle formulations, were designed, synthesized, and systematically investigated as potential photosensitizers for photodynamic therapy. The obtained novel triazine-BODIPY derivatives were fully characterized by NMR, mass spectrometry, and single-crystal X-ray diffraction analysis. Particle sizes of nanomicelles were determined by DLS and zeta potential measurement data. Chemical assays demonstrated that the compounds generated singlet oxygen in organic solvents under controlled light irradiation, while their micellar assemblies produced singlet oxygen in aqueous media. The in vitro photodynamic therapy (PDT) efficiencies of the nanomicelles against cancer cell lines (PC3 and DU145) were evaluated, and significant cell death was observed at nanomolar (nM) concentrations under controlled light irradiation. Confocal fluorescence imaging further confirmed the efficient cellular uptake of the nanomicelles in cancer cells. Apoptosis studies further confirmed that the nanomicelles induce cell death predominantly through activation of the extrinsic caspase-8 pathway. Overall, these findings highlight triazine-BODIPY-based nanomicelles as promising, water-compatible photosensitizers for photodynamic cancer therapy.