Second Near-infrared Light-activatable CO nanogenerator for enhanced cancer Photo-theranostics

Carbon monoxide (CO) has received substantial attention for its many beneficial functions in multiple major diseases. However, precise delivery and controllable release of CO are crucial for CO therapy in cancer but remain technically challenging. Herein, an NIR-II light-controlled CO nanogenerator is described as a new cancer photo-theranostic (Pd@PdCO-MOF) via photoacoustic imaging guided photothermal/CO-combined therapy. This nanogenerator is based on an NIR-II-photothermal palladium nanosheet core and a porphyrin-palladium metal-organic framework (Pd-MOF) shell, which can coordinate/load large amounts of CO with single-atom palladium. Meanwhile, the obtained photo-theranostic exhibited excellent release of CO on demand after NIR-II photoactivation. The produced CO molecules successfully increased the sensitivity of cancer cell to photo-thermal therapy (PTT). Mechanistically, the CO-assisted PTT efficiently inhibited cancer development by decreasing the intracellular ATP levels, downregulating heat shock protein expression, increasing the expression of cytochrome C, and subsequently activating the apoptosis pathway. Guided by photoacoustic imaging, the obtained Pd@PdCO-MOF nanoplatform demonstrated high therapeutic efficacy in vitro and in vivo through the photothermal-CO combination therapy, which may provide a new strategy for cancer theranostics.