Pt‐Decorated Gold Nanoflares for High‐Fidelity Phototheranostics: Reducing Side‐Effects and Enhancing Cytotoxicity toward Target Cells

Abstract Functionalized with the Au−S bond, gold nanoflares have emerged as promising candidates for theranostics. However, the presence of intracellular abundantly biothiols compromises the conventional Au−S bond, leading to the unintended release of cargoes and associated side‐effects on non‐target cells. Additionally, the hypoxic microenvironment in diseased regions limits treatment efficacy, especially in photodynamic therapy. To address these challenges, high‐fidelity photodynamic nanoflares constructed on Pt‐coated gold nanoparticles (Au@Pt PDNF) were communicated to avoid false‐positive therapeutic signals and side‐effects caused by biothiol perturbation. Compared with conventional photodynamic gold nanoflares (AuNP PDNF), the Au@Pt PDNF were selectively activated by cancer biomarkers and exhibited high‐fidelity phototheranostics while reducing side‐effects. Furthermore, the ultrathin Pt‐shell catalysis was confirmed to generate oxygen which alleviated hypoxia‐related photodynamic resistance and enhanced the antitumor effect. This design might open a new venue to advance theranostics performance and is adaptable to other theranostic nanomaterials by simply adding a Pt shell.