Mitochondria-targeted nanotheranostic: Harnessing single-laser-activated dual phototherapeutic processing for hypoxic tumor treatment

Summary Realizing maximum tumor suppression along with preventing tumor regrowth by optimizing the photon usage in phototherapy remains a major challenge. Herein, a mitochondria-targeted phototheranostic nanoformulation (MsPDTT NPs) was prepared from a molecular theranostic encapsulated into phospholipids. Notably, under single 690 nm laser excitation, MsPDTT NPs can perform dual-mode photoacoustic and near-infrared fluorescence imaging and potent photodynamic therapy/photothermal therapy (PDT/PTT) because of efficient excited-state deactivation pathways (through radiative and energy transfer to generate reactive oxygen species and non-radiative relaxation). The reference RsPDTT NPs lacking the mitochondria-targeting feature exhibit only the PTT property. Based on biological results, the MsPDTT NP therapeutic response can be switched to PDT and PTT under normoxic and hypoxic environments and maximize the overall efficacy of phototherapies without any noticeable side effects. The current findings suggest the potential of using simultaneous PDT/PTT with proper photon utilization as a promising theranostic approach for hypoxic tumor photoablation.