Mitochondrial Targeted Composite Nanoplatform Activated by a Single NIR Laser for Enhanced Synergistic PTT, PDT, and Chemotherapy

The combinations of phototherapeutic modalities with chemotherapy represent an innovative antitumor strategy. Herein, we constructed a NIR laser regulated nanoplatform (PTE@TPP-NM(DOX/IR780)) via the self-assembly process of PEG-b-PCL modified with mitochondrial targeting triphenylphosphine (TPP), reactive oxygen species (ROS)-sensitive polymer (PTE), DOX, and IR780. Under 808 nm laser irradiation, IR780 in PTE@TPP-NM(DOX/IR780) generated abundant reactive oxygen species (ROS) and heat for photothermal therapy (PTT) and photodynamic therapy (PDT), while ROS oxidized PTE to release DOX for chemotherapy. The signal 808 nm laser could effectively regulate PTT, PDT, and chemotherapy in real-time, enhancing the synergistic efficacy. PTE@TPP-NM(DOX/IR780) could result in depolarization of the mitochondrial membrane and inhibition of the expression of heat shock proteins to amplify antitumor effect. Enhanced therapeutic effect was demonstrated via in vivo and in vitro experiment. This study provided a promising strategy for the design of multifunctional nanocarriers to address the limitation of combined therapy.