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MRSA biofilms are often resistant to multiple antimicrobial strategies, mainly due to the existence of a compact protective barrier; thus, protecting themselves from the innate immune system and antibiotic treatment via limited drug penetration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A hierarchically structured hydrogen sulfide (H<jats:sub>2<\/jats:sub>S)-releasing nano-disinfectant was presented, which was composed of a zinc sulfide (ZnS) core as a H<jats:sub>2<\/jats:sub>S generator and indocyanine green (ICG) as a photosensitizer. This nano-disinfectant (ICG-ZnS NPs) sensitively responded to the biofilm microenvironment and demonstrated efficient eradication of MRSA biofilms via a synergistic effect of Zn<jats:sup>2+<\/jats:sup>, gas molecule-mediated therapy, and hyperthermia. Physically boosted by released H<jats:sub>2<\/jats:sub>S and a near-infrared spectroscopy-induced hyperthermia effect, ICG-ZnS NPs destroyed the compactness of MRSA biofilms showing remarkable deep-penetration capability. Moreover, on-site generation of H<jats:sub>2<\/jats:sub>S gas adequately ameliorated excessive inflammation, suppressed secretion of inflammatory cytokines, and expedited angiogenesis, therefore markedly accelerating the in vivo healing process of cutaneous wounds infected with MRSA biofilms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>ICG-ZnS NPs combined with NIR laser irradiation exhibited significant anti-biofilm activity in MRSA biofilms, can accelerate the healing process through deep-penetration and anti-inflammatory effectuation. The proposed strategy has great potential as an alternative to antibiotic treatment when combating multidrug-resistant bacterial biofilms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Graphical Abstract<\/jats:title><\/jats:sec>","DOI":"10.1186\/s12951-022-01262-7","type":"journal-article","created":{"date-parts":[[2022,1,29]],"date-time":"2022-01-29T11:03:39Z","timestamp":1643454219000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["pH-responsive hierarchical H2S-releasing nano-disinfectant with deep-penetrating and anti-inflammatory properties for synergistically enhanced eradication of bacterial biofilms and wound infection"],"prefix":"10.1186","volume":"20","author":[{"given":"Yue","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianxiang","family":"Yue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenting","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aidi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengying","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyue","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dandan","family":"Bao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanzhu","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-Gang","family":"Piao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,1,29]]},"reference":[{"key":"1262_CR1","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1002\/cmdc.202000677","volume":"16","author":"S Cascioferro","year":"2021","unstructured":"Cascioferro S, Carbone D, Parrino B, Pecoraro C, Giovannetti E, Cirrincione G, Diana P. 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