Biomimetic sulfur dioxide-releasing Fe single atom Nanozyme for boosting antibacterial infection therapy by amplifying bacterial Ferroptosis-like death.

Sulfur dioxide (SO2) has been recognized as the fourth gasotransmitter and holds great promise for antibacterial infection therapy. However, near-infrared (NIR) laser-triggered SO2-releasing nanoplatforms remain underdeveloped. Herein, a raspberry-like mesoporous Fe single atom nanozyme (Fe mSAz) with NIR-II laser-reinforced peroxidase (POD)-like activity was synthesized to construct a smart SO2-controlled release platform. To this end, the SO2 donor 2,4-dinitrobenzenesulfonyl chloride (DN) was first loaded into the pores of Fe mSAz with the aid of a phase change material (PCM), followed by surface functionalization with a macrophage membrane (M), yielding a biomimetic SO2-releasing nanozyme denoted Fe mSAz@DN@M. Upon 1064 nm laser irradiation, the photothermal effect of Fe mSAz@DN@M first induced melting of the PCM to release DN, which subsequently triggered a burst of SO2 generation. In the meantime, 1064 nm laser irradiation enhanced the POD-like activity of Fe mSAz by generating a substantial amount of hydroxyl radical (ꞏOH). As a result, Fe mSAz@DN@M exhibited robust antibacterial efficacy through a synergistic SO2/ꞏOH effect. Mechanistic studies revealed that SO2 and ꞏOH synergistically suppressed bacterial activity by amplifying bacterial ferroptosis-like death. Furthermore, due to macrophage membrane functionalization, Fe mSAz@DN@M achieved highly effective targeting of subcutaneous tissues infected with Staphylococcus aureus (S. aureus) in mice. Consequently, Fe mSAz@DN@M also demonstrated excellent in vivo antibacterial infection efficacy through the synergistic SO2 and ꞏOH effect, which not only eradicated the infectious bacteria but also subsequently induced repolarization of anti-inflammatory M2 macrophages to promote wound healing.