Cu2- xS Nanocrystals Cross-Linked with Chlorin e6-Functionalized Polyethylenimine for Synergistic Photodynamic and Photothermal Therapy of Cancer.

Achieving an integrated system for combinational therapy of cancer with enhanced efficacy is always a challenge. A multifunctional system (CCeT nanoparticles (NPs)) for a synergistic photodynamic and photothermal cancer therapy was successfully developed. This system is composed of Cu2- xS nanoclusters functionalized with chlorin e6 (Ce6)-conjugated branched polyethylenimine (PEI-Ce6) and mitochondria-targeting 3-(carboxypropyl)triphenylphosphonium bromide (TPP-COOH). The colocalization of the resulted CCeT NPs inside the mitochondria of cancer cells was proven. The CCeT NPs exhibited significant photodynamic therapy (PDT) efficacy due to efficient singlet oxygen (1O2) generation triggered by a 630 nm laser. This system also showed excellent photothermal conversion capability upon the irradiation of 808 nm laser for photothermal therapy (PTT). In particular, the platform achieved nearly 100% inhibitory rate of the tumor growth in vivo through combinational PDT and PTT. Thus, the CCeT NPs could efficiently inhibit the tumor growth in vitro and in vivo by combinational PDT and PTT, offering synergistic therapeutic efficiency as compared to PTT or PDT alone.