Programmable NIR-II Photothermal-Enhanced Starvation-Primed Chemodynamic Therapy using Glucose Oxidase-Functionalized Ancient Pigment Nanosheets

Chemodynamic therapy (CDT) has attracted considerable attention recently, but the poor reaction kinetics restrict its practical utility in clinic. Herein, glucose oxidase (GOx) functionalized ancient pigment nanosheets (SrCuSi4O10, SC) for programmable near-infrared II (NIR-II) photothermal-enhanced starvation primed CDT is developed. The SC nanosheets (SC NSs) are readily exfoliated from SC bulk suspension in water and subsequently functionalized with GOx to form the nanocatalyst (denoted as SC@G NSs). Upon laser irradiation, the photothermal effect of SC NSs can enhance the catalytic activity of GOx for NIR-II photothermal-enhanced starvation therapy, which effectively eliminates intratumoral glucose and produces abundant hydrogen peroxide (H2O2). Importantly, the high photothermal-conversion efficiency (46.3%) of SC@G NSs in second biological window permits photothermal therapy of deep-seated tumors under the guidance of NIR-II photoacoustic imaging. Moreover, the acidity amplification due to gluconic acid generation will in turn accelerate the degradation of SC NSs, facilitating the release of strontium (Sr) and copper (Cu) ions. Both the elevated H2O2 and the released ions will prime the Cu2+/Sr2+-H2O2 reaction for enhanced CDT. Thus, a programmable NIR-II photothermal-enhanced starvation primed CDT is established to combat cancer with minimal side effects.