Synergistic Effects in Matrix-Embedded Alloy Nanoclusters: Advanced Type-I Photosensitizers for Theranostics.

A combination of biomedical imaging and photodynamic therapy (PDT) in a single nanomaterial would be a breakthrough in nanomedicine. However, devising a single photosensitizer capable of efficient PDT without requiring an external oxygen source under typically hypoxic tumor conditions, combined with high photostability, biocompatibility, and renal clearance, remains a challenge. Atomically precise ultrasmall (<2 nm) gold nanoclusters (AuNCs) are emerging as potential multifunctional biomedicines, encompassing imaging, diagnosis, and therapy in a single nanoplatform. Herein, we report bioderived cellulose nanocrystal-supported gold nanoclusters (CNC-AuNCs) with selective mono or multiheteroatom (Ag, Pd, and Pt) substitution at the core of the nanoclusters. The replacement of one or more gold atoms significantly modulates their emission wavelengths, photoluminescence quantum yields, as well as excited-state relaxation kinetics. These materials can easily penetrate the cells, accumulating in the cytoplasm and emitting bright luminescence. While the nanocomposites are highly biocompatible, they can produce reactive oxygen species (ROS) through the formation of free radicals (O2-· and ·OH) upon exposure of light. The synergistic effect of the light absorption by the matrix and the diverse excited-state relaxation pathways of the nanoclusters results in the efficient generation of ROS in variable concentrations, ultimately leading to the complete destruction of targeted cancer cells via Type-I photodynamic effect. The optimal ROS efficacy combined with minimal cytotoxicity suggests a universal strategy for developing strong PDT-I agents, paving the way for versatile nanomaterials in theranostic applications.