Rational design of molecular phototheranostic platform for NIR-II fluorescence imaging guided chemodynamic-photothermal combined therapy

The strategy of synergetic chemodynamic treatment (CDT) and photothermal therapy (PTT) to improve the anticancer effect has been a hot spot in the field of biomedicine. Herein, a high-performance near-infrared II (NIR-II) fluorescence imaging-guided molecular phototheranostic platform (IR-FE-Fc@DSPE-S-S-PEG) was designed via a convenient strategy. IR-FE-Fc@DSPE-S-S-PEG can serve as a PTT agent to kill cancer cells under near-infrared laser (808 nm) irradiation and a CDT agent to convert the endogenously less reactive H2O2 into the harmful •OH, simultaneously deplete the glutathione (GSH) to achieve an amplified CDT as well. Notably, PTT-induced hyperthermia can further enhance the CDT effect, achieving a synergistic PTT/CDT therapy. Due to the enhanced permeability and retention (EPR) effect and the high GSH microenvironment of the tumor, IR-FE-Fc@DSPE-S-S-PEG exhibited much higher tumor accumulation revealed by NIR-II fluorescence imaging. More importantly, IR-FE-Fc@DSPE-S-S-PEG efficiently damages tumorous tissues without inducing side effects to normal tissues under 808 nm laser irradiation. This work has proposed an alternative PTT-CDT combined therapy platform based on a rational design of disintegrable NIR-II fluorescence imaging-guided molecular for effective tumor treatment.