Sophisticated plasmon-enhanced photo-nanozyme for anti-angiogenic and tumor-microenvironment-responsive combinatorial photodynamic and photothermal cancer therapy

In the exploitation of nanozymes possessing intrinsic enzyme-like activities for cancer therapy, minor focus has been devoted to plasmonic nanostructures with localized surface plasmon resonance (LSPR)-driven properties. Here, we report the application of unique peroxidase-mimicking plasmonic photo-nanozymes coupling tumor-microenvironment-responsive reactive oxygen species generation with photothermal effect for effective combinatorial therapy. The well-defined anisotropic photo-nanozyme is synthesized by selectively depositing Pd nanoparticles on the tips of gold nanobypyramids. Intrinsic peroxidase-like properties with 1.5-fold-activity enhancement under photoexcitation are ascribed to a Pd-induced hot electrons/holes separation with efficient H₂O₂ decomposition. The LSPR-induced photocatalytic/photothermal combinatorial effects are remarkably enhanced upon H₂O₂ addition, critically suppressing the cell survival rate under near-infrared light. An effective decomposition of cell-signaling H₂O₂ additionally reveals prominent expression hindrance of vascular endothelial growth factor and hypoxia-inducible factor 1α. Our seminal findings uncover an interrelation between LSPR-induced phenomena and biomimetic fingerprints, valuable to overcome the shortcomings of conventional photodynamic therapy.