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However, current H\n                    <jats:sub>2<\/jats:sub>\n                    S delivery approaches lack sufficient specificity against inflammatory response. Herein, regarding the overexpressed aminopeptidase N (APN) at the inflammation sites, an APN\u2010activated self\u2010immolative carbonyl sulfide (COS)\/H\n                    <jats:sub>2<\/jats:sub>\n                    S donor (\n                    <jats:bold>AlaCOS<\/jats:bold>\n                    ) was developed for inflammatory response\u2010specific H\n                    <jats:sub>2<\/jats:sub>\n                    S delivery. The compound showed sustained H\n                    <jats:sub>2<\/jats:sub>\n                    S generation upon APN activation in the presence of carbonic anhydrase (CA), and the responsiveness could be well regulated by modulating the amino acid sequence. Due to the inflammatory response\u2010specific sustained H\n                    <jats:sub>2<\/jats:sub>\n                    S delivery,\n                    <jats:bold>AlaCOS<\/jats:bold>\n                    provided potent anti\u2010inflammatory capability, which was further validated by RNA sequencing. In vivo experiments on a full\u2010thickness cutaneous wound murine model also showed the strong promoting effect on wound healing, mainly due to the regulation of the inflammatory response by\n                    <jats:bold>AlaCOS<\/jats:bold>\n                    . By introducing a caged coumarin fluorophore to the molecular architecture, self\u2010reporting fluorescence could be generated accompanied with APN\u2010mediated COS\/H\n                    <jats:sub>2<\/jats:sub>\n                    S release, which achieved the visualization of H\n                    <jats:sub>2<\/jats:sub>\n                    S delivery in vitro and in vivo. This work not only offers a useful tool for studying the bioactivity of H\n                    <jats:sub>2<\/jats:sub>\n                    S on inflammation, but also provides new insights for developing novel therapies to cope with inflammation\u2010associated diseases.\n                  <\/jats:p>","DOI":"10.1002\/anie.202423527","type":"journal-article","created":{"date-parts":[[2025,1,16]],"date-time":"2025-01-16T04:39:55Z","timestamp":1737002395000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Aminopeptidase N\u2010Activated Self\u2010immolative Hydrogen Sulfide Donor for Inflammatory Response\u2010Specific Wound Healing"],"prefix":"10.1002","volume":"64","author":[{"given":"Fan","family":"Rong","sequence":"first","affiliation":[{"name":"Engineering Research Center of Cell &amp; Therapeutic Antibody Shanghai Frontiers Science Center of Drug Target Identification and Delivery School of Pharmaceutical Sciences Shanghai Jiao Tong University  Shanghai 200240 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenxin","family":"Bao","sequence":"additional","affiliation":[{"name":"Engineering Research Center of Cell &amp; Therapeutic Antibody Shanghai Frontiers Science Center of Drug Target Identification and Delivery School of Pharmaceutical Sciences Shanghai Jiao Tong University  Shanghai 200240 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanyi","family":"Li","sequence":"additional","affiliation":[{"name":"Engineering Research Center of Cell &amp; Therapeutic Antibody Shanghai Frontiers Science Center of Drug Target Identification and Delivery School of Pharmaceutical Sciences Shanghai Jiao Tong University  Shanghai 200240 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxuan","family":"Ge","sequence":"additional","affiliation":[{"name":"Engineering Research Center of Cell &amp; Therapeutic Antibody Shanghai Frontiers Science Center of Drug Target Identification and Delivery School of Pharmaceutical Sciences Shanghai Jiao Tong University  Shanghai 200240 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wangyang","family":"Zhu","sequence":"additional","affiliation":[{"name":"Engineering Research Center of Cell &amp; Therapeutic Antibody Shanghai Frontiers Science Center of Drug Target Identification and Delivery School of Pharmaceutical Sciences Shanghai Jiao Tong University  Shanghai 200240 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Hao","sequence":"additional","affiliation":[{"name":"Engineering Research Center of Cell &amp; Therapeutic Antibody Shanghai Frontiers Science Center of Drug Target Identification and Delivery School of Pharmaceutical Sciences Shanghai Jiao Tong University  Shanghai 200240 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaxue","family":"Zhao","sequence":"additional","affiliation":[{"name":"Engineering Research Center of Cell &amp; Therapeutic Antibody Shanghai Frontiers Science Center of Drug Target Identification and Delivery School of Pharmaceutical Sciences Shanghai Jiao Tong University  Shanghai 200240 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunsheng","family":"Yuan","sequence":"additional","affiliation":[{"name":"Engineering Research Center of Cell &amp; Therapeutic Antibody Shanghai Frontiers Science Center of Drug Target Identification and Delivery School of Pharmaceutical Sciences Shanghai Jiao Tong University  Shanghai 200240 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6729-7230","authenticated-orcid":false,"given":"Yin","family":"Wang","sequence":"additional","affiliation":[{"name":"Engineering Research Center of Cell &amp; Therapeutic Antibody Shanghai Frontiers Science Center of Drug Target Identification and Delivery School of Pharmaceutical Sciences Shanghai Jiao Tong University  Shanghai 200240 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,2,7]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07201"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-386456-7.01808-6"},{"key":"e_1_2_8_3_1","unstructured":"\u00a0"},{"key":"e_1_2_8_4_2","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2012.4612"},{"key":"e_1_2_8_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0675-0"},{"key":"e_1_2_8_6_1","unstructured":"\u00a0"},{"key":"e_1_2_8_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10787-023-01366-y"},{"key":"e_1_2_8_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2017.10.010"},{"key":"e_1_2_8_9_2","volume":"346","author":"Day R. 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