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The nonselective bactericidal nature of antibiotics and low customization rate of probiotic supplementation in existing treatments lead to AV recurrence. Here, a drug delivery strategy is proposed that works with the changing dynamics of the bacterial flora. In particular, a core\u2013shell nanogel (<jats:bold>CSNG<\/jats:bold>) is designed to encapsulate prebiotic inulin and antimicrobial peptide Cath 30. The proposed strategy allows for the sequential release of both drugs using gelatinase produced by AV pathogenic bacteria, initially selectively killing pathogenic bacteria and subsequently promoting the proliferation of beneficial bacteria in the vagina. In a simulated infection environment in vitro, the outer layer of <jats:bold>CSNGs<\/jats:bold>, Cath 30 is rapidly degraded and potently killed the pathogenic bacterium <jats:italic>Staphylococcus aureus<\/jats:italic> at 2\u20136\u00a0h. <jats:bold>CSNGs<\/jats:bold> enhances proliferation of the beneficial bacterium <jats:italic>Lactobacillus crispatus<\/jats:italic> by more than 50% at 24\u00a0h. In a rat AV model, the drug delivery strategy precisely regulated the bacterial microenvironment while controlling the inflammatory response of the vaginal microenvironment. This new treatment approach, configured on demand and precisely controlled, offers a new strategy for the treatment of vaginal diseases.<\/jats:p>","DOI":"10.1002\/adhm.202202432","type":"journal-article","created":{"date-parts":[[2023,2,6]],"date-time":"2023-02-06T16:45:11Z","timestamp":1675701911000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Controlled Cascade\u2010Release and High Selective Sterilization by Core\u2013Shell Nanogels for Microenvironment Regulation of Aerobic Vaginitis"],"prefix":"10.1002","volume":"12","author":[{"given":"Xinxin","family":"Wang","sequence":"first","affiliation":[{"name":"Shandong Key Laboratory of Proteins and Peptides Pharmaceutical Engineering Shandong Universities Key Laboratory of Biopharmaceuticals School of Life Science and Technology Weifang Medical University  Weifang Shandong 261053 P. R. 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