Near-infrared light activated photosensitizer with specific imaging of lipid droplets enables two-photon excited photodynamic therapy

Abstract

Two-photon excited phototherapy has attracted considerable attention due to its advantages such as deeper penetration depth and higher spatial resolution. The lack of a high-performance photosensitizer with large two-photon absorption cross-sections and specific targeting ability makes the efficacy of phototherapy in the treatment of cancer unsatisfactory. Here, a new BODIPY-derived photosensitizer 6DBF₂ is designed with two-photon photosensitization for two-photon excited photodynamic therapy in vivo. 6DBF₂ possesses good two-photon absorption and efficient ¹O₂ generation upon near-infrared laser excitation. Excellent targeting specificities to lipid droplets of 6DBF₂ without any encapsulation or modification at a low working concentration of 0.1 μM is in favor of efficient photodynamic therapy. In vitro cancer cell ablation and in vivo tumor ablation inside mice models upon two-photon irradiation in NIR demonstrate the outstanding therapeutic performance of 6DBF₂ in two-photon excited photodynamic therapy. This work thus discusses a rare example of lipid droplets targeting two-photon excited photodynamic therapy for deep cancer tissue imaging and treatment under near-infrared light irradiation.