Facile Synthesis of Designer Shape-Defined Mesoporous Metal Nanoenzymes as Therapeutics for Diseases Involving Excessive Oxidative Stress

Mesoporous metal nanomaterials (MMNs) have gained interest in biomedicine for their unique properties, but their potential is limited by the predominance of spherical shapes and the neglect of morphological effects on biological activity, which hinders the reasonable evaluation of morphology-dependent enzyme-like activities and biological behaviors and its further biomedical applications. It is therefore imperative to find an effective and facile method to design and prepare MMNs with novel, well-defined morphologies. Herein, we fabricated 3 mesoporous platinum nanoenzymes including sphere, rod, and bipyramid topologies [Au@mesoPt sphere, Au@mesoPt rod, and Au@mesoPt bipyramid nanoparticles (NPs), respectively] via a facile atomic layer deposition method using gold NPs (Au NPs) as the templated cores and Pluronic F127 as a structure-directing agent. The obtained Au@mesoPt NPs could enhance cellular uptake efficiency and prolong blood elimination half-lives, which helped more cancer cell spheroid permeation and accumulation at the disease sites post-injection. Au@mesoPt NPs could obviously alleviate atherosclerosis through reactive oxide species (ROS) scavenge due to its catalase-like activity and inhibition of pro-inflammatory cytokine release. Due to the role of metal nanoenzymes containing high-order-number (<i>Z</i>) elements as radiosensitizers, Au@mesoPt NPs have a distinct radiosensitizing on pancreatic cancer treatment. Among the shapes, Au@mesoPt bipyramids showed the best therapeutic efficacy in treating atherosclerosis and pancreatic cancer, likely due to their high aspect ratio, irregular surface, and anisotropy, which favor blood flow and cellular uptake. The tunable synthesis of shape-defined MMNs bodes well for other areas of application, including biosensors, surface-enhanced Raman scattering, surface plasmon resonance, hydrogen storage, catalysis, and electrotherapy.