Tuning a consistent near-infrared photo-initiated multimodal tumor strategy based on the core–shell structure of gold star@PB@CuS nanoparticles

Abstract

Anisotropic gold nanostars are near-infrared (NIR) absorbing photosensitizers applied in photothermal therapy (PTT) and photodynamic therapy (PDT). However, the thermodynamic instability of the gold nanostars leading to passivation limits their anti-tumor efficacy in addressing spreading and metastatic tumors. Herein gold star@PB@CuS (GPC) nanoparticles with a core–shell structure were designed and fabricated to address the shortcomings above and achieve multimodal anti-tumor treatment. GPC exhibits a broader absorption peak (810 nm) at the near-infrared region (NIR) through the synergistic effect, achieving excellent photothermal conversion efficiency and stability along with stronger photoacoustic (PA) imaging. The high tunable plasmon resonances of gold nanostars enable them to optimize the localized surface plasmon resonance (LSPR) effect through adjustments in their shape and size. This ensures that the laser wavelengths used for PTT and PDT processes of GPC are coherent at 808 nm (in the so-called “first bio-window”), without significant passivation. Simultaneously, we found that GPC further introduced chemodynamic therapy (CDT) by enabling glutathione (GSH) depletion, Fenton-like reactions, and self-supplied O₂ to assist type-I PDT breaking in hypoxia and over expressed the GSH tumor microenvironment (TME). The endogenous and exogenous triggered nanotherapeutic platform PTT/PDT/CDT enables a complete ablation of 4T1 tumors within the first bio-window, showcasing enhanced photo-therapeutic efficacy and addressing critical challenges in current anti-tumor strategies.