NIR-II Light-Activated Gold Nanocapsules for CO-Assisted Photothermal-Thermodynamic Synergistic Cancer Therapy

Photothermal therapy (PTT) based on a second near-infrared (NIR-II, 1000-1700 nm) light source holds great promise in the field of tumor treatment. However, hyperthermia-induced heat shock protein (HSP) expression and limited therapeutic efficacy remain the major challenges for PTT. Herein, a NIR-II laser-responsive nanocapsule PC/AC@GR@HA (abbreviated as P/A@G@H) was designed for carbon oxide (CO)-assisted tumor PTT combined with thermodynamic therapy (TDT). P/A@G@H was constructed by loading the CO storage polymer mPEG(CO) (PC) along with the free radical initiator 4,4'-azobis(4-cyanovaleric acid) (AC) into a gold hollow nanorod (GR), followed by the surface coating of hyaluronic acid (HA). After accumulating in tumor tissue through the active targeting of HA, P/A@G@H can quickly cause local hyperthermia upon 1064 nm laser irradiation and lead to cell damage by GR-mediated PTT. Moreover, the loaded PC can react with in situ H₂O₂ to produce CO, which inhibits the PTT-induced HSP90 expression. This can effectively weaken the heat resistance of tumor cells and enhance the PTT effect. Additionally, as a thermally decomposable radical initiator, AC can turn to toxic free radicals to ablate tumor cells via TDT under hyperthermia. Our research demonstrates that the synergistic strategy combining CO-assistance and TDT can effectively augment the ultimate therapeutic outcome of PTT, and the integrated nanocapsule P/A@G@H could be a powerful weapon for tumor suppression based on NIR-II light.