Intrinsic Near‐Infrared‐II Fluorescent Nanozymes Support High‐Resolution Imaging and Tumor Catalytic Immunotherapy

Abstract

ABSTRACT Nanozymes hold considerable promise for in vivo therapy due to their stable and versatile enzyme‐mimicking activities. However, real‐time tracking of their dynamics with high spatiotemporal resolution and ensuring biosafety remain challenging. Here, we report a class of single‐component, metal‐free autofluorescent nanozymes (AFNZs) that simultaneously exhibit ultrabright second near‐infrared (NIR‐II) fluorescence (FL) and potent multienzyme‐like activities. By precisely controlling sulfur/nitrogen (S/N) stoichiometry during the solvothermal conversion of cyanine precursors, we developed intrinsically emissive nanozymes with high‐brightness NIR‐II FL (quantum yield >1.4%, maximum emission wavelength >1100 nm) among metal‐free nanozyme systems, achieving a 20‐fold enhancement over their precursors. The optimized AFNZs exhibit strong peroxidase (POD)‐, catalase (CAT)‐, and oxidase (OXD)‐like activities, enabling high‐contrast in vivo imaging and catalytic tumor therapy. Mechanistic studies suggest that the enhanced FL is associated with restricted intramolecular motion (RIM). These nanozymes support deep‐tissue tumor imaging (∼8 mm) and high‐resolution angiography (∼30 µm), substantially outperforming their precursors and the clinical contrast agent indocyanine green (ICG). Furthermore, they enable precise tumor margin identification, image‐guided resection of microtumors (< 5 mm), and real‐time monitoring of catalytic immunotherapy associated with autophagic flux disruption and immune activation. This work offers a stoichiometry‐guided strategy for constructing intrinsically fluorescent metal‐free AFNZs for image‐guided catalytic therapy.