A self-assembled nanophotosensitizer targets lysosomes and induces lysosomal membrane permeabilization to enhance photodynamic therapy

Abstract

We report the self-assembly of amphiphilic BDQ photosensitizers into lysosome-targeting nanophotosensitizer BDQ-NP for highly effective photodynamic therapy (PDT). Molecular dynamics simulation, live cell imaging, and subcellular colocalization studies showed that BDQ strongly incorporated into lysosome lipid bilayers to cause continuous lysosomal membrane permeabilization. Upon light irradiation, the BDQ-NP generated a high level of reactive oxygen species to disrupt lysosomal and mitochondrial functions, leading to exceptionally high cytotoxicity. The intravenously injected BDQ-NP accumulated in tumours to achieve excellent PDT efficacy on subcutaneous colorectal and orthotopic breast tumor models without causing systemic toxicity. BDQ-NP-mediated PDT also prevented metastasis of breast tumors to the lungs. This work shows that self-assembled nanoparticles from amphiphilic and organelle-specific photosensitizers provide an excellent strategy to enhance PDT.