Dual-targeted multifunctional ultrasmall sulfur-AuPt nanocomposite for NIR-II photothermal enhanced chemodynamic therapy.

In the field of nanozyme-based tumor therapy, AuPt nanomaterials have garnered significant attention due to their biocompatibility, photothermal efficiency, and catalytic activity. While alloying with other metals (e.g., Cu, Ni, Pd) can further boost enzyme activity and therapeutic effect, it may typically compromise biocompatibility. To address this limitation, we report the development of ultrasmall (∼3.4 nm) sulfur-element composited AuPt conjugated with hyaluronic acid-polyethylene glycol-triphenylphosphine (S-AuPt/HPT) for NIR-II photothermal-enhanced chemodynamic therapy (CDT). The incorporation of sulfur not only improves colloidal stability and biocompatibility, but also creates abundant active sites and ion pairs. Compared with pure AuPt, ultrasmall S-AuPt exhibits enhanced NIR-II absorption and markedly superior peroxidase-like (POD-like) and glutathione oxidase (GSH-OXD) activities. Within cells, S-AuPt/HPT generated a large amount of hydroxyl radicals (·OH) to induce damage, while consuming glutathione (GSH) to reduce tumor resistance. In addition, S-AuPt/HPT demonstrates dual-targeting capability toward CD44 receptors and mitochondria, which further enhances the therapeutic efficiency. In vitro and in vivo studies revealed that S-AuPt/HPT exhibits outstanding biocompatibility (86.9 % cell viability at a high concentration of 600 μg/mL), as well as a remarkable 94.2 % tumor suppression rate. This study demonstrates a design strategy that prioritises biosafety to improve the treatment performance of the material.