Dual-selective photodynamic therapy with a mitochondria-targeted photosensitizer and fiber optic cannula for malignant brain tumors

Abstract

Among brain tumors, glioblastoma multiforme (GBM) is the most common and aggressive form (WHO grade IV) with a median survival of only 14.6 months in adults. Photodynamic therapy (PDT) is a combination of a photosensitizer (PS), light and molecular oxygen, and considered a promising treatment for GBM. Therapeutic outcomes of PDT rely on ROS generation in a tumor microenvironment, which can be controlled with dual selectivity by localization of the photosensitizer and confinement of light to the targeted tumor microenvironment. We previously demonstrated the photodynamic anticancer efficacy of mitochondrial-targeted photosensitizer-loaded albumin nanoparticles (PS@chol-BSA NPs). In this study, the photodynamic therapeutic effect of PS@chol-BSA NPs was further enhanced by confinement of light using a fiber optic cannula in orthotopic GBM-xenografted mice. In vitro cellular uptake and phototoxicity of PS@chol-BSA NPs were evaluated in brain tumor (U87MG) and endothelial (bEnd.3) cells. In vivo biodistribution was determined by an in vivo imaging system (IVIS) and the photodynamic efficacy was evaluated with confined laser irradiation. PS@chol-BSA NPs showed higher cellular uptake and phototoxicity in U87MG cells than in bEnd.3 cells. PS@chol-BSA NPs showed a brain tumor accumulation of 0.2%ID within 2 h and remain in the brain tumor for 22 h. When compared to the control group, there was remarkable suppression in tumor growth by laser irradiation with and without the fiber optic cannula at a dose of 1 mg kg⁻¹, in which significant tumor suppression up to 40% was observed with confined laser irradiation. Together, dual-selective photodynamic therapy with a mitochondria-targeted photosensitizer and fiber optic cannula provides a promising therapeutic strategy for malignant brain tumors.