Nanozyme-like single-atom catalyst combined with artesunate achieves photothermal-enhanced nanocatalytic therapy in the near-infrared biowindow

Selectively generating active free radical (AFR) in tumor microenvironment (TME) can promote irre-versible oxidation of biomolecules and damage tumor cells, resulting in effective tumor inhibition. How-ever, therapeutic efficacy of AFR-based tumor suppression approaches is often limited by insufficient amount of H2O2 or O 2 within TME. To overcome this obstacle, we design a pH/photothermal dual respon-sive nanosystem (PFeSA@AS) for combined photothermal and nanocatalytic therapy in the near-infrared biowindow. Here the Fe single-atom dispersed N, S-doped carbon nanosheets (FeSA) nanozyme is dis-persed by phospholipid-polyethylene glycol-amine (DSPE-PEG-NH2), and further loads artesunate (AS) via an amide reaction. Upon 808-nm laser irradiation in TME, the AS is released and further be cat-alyzed by the FeSA nanozyme to produce cytotoxic C-centered AFRs, and further be accelerated due to the photothermal conversion performance of FeSA (23.35%). The nanocatalytic process of FeSA nanozyme is realized by density functional theory (DFT). The tumor inhibition rates of a CT26 xenograft model is 92% through a photothermal-enhanced nanocatalytic synergistic therapy, and negligible systematic toxi-city is observed. This work offers a potential paradigm of multifunctional single atomic catalysts (SACs) for enhancing tumor nanocatalytic therapy.Statement of significance We designed a pH/photothermal dual responsive nanosystem (PFeSA@AS) for nanocatalytic therapy: (1) the nanosystem responsively releases AS under 808-nm laser irradiation in TME; (2) FeSA in the nanosys-tem can act as heme mimetic to convert AS into high cytotoxic C-centered free radicals for nanocatalytic therapy; (3) the photothermal conversion performance of FeSA further enhances the catalytic process to yield abundant AFR. Both in vitro and in vivo results demonstrate that this nanosystem can efficiently inhibit tumor growth through a photothermal-enhanced nanocatalytic synergistic therapy.(c) 2022 Published by Elsevier Ltd on behalf of Acta Materialia Inc.