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Although nanomedicines are recognized as promising anti\u2010inflammatory medicines, their clinical application is limited by their high cost and unpredictable safety risks. This study reveals that two natural phytochemicals, berberine (BBR) and hesperetin (HST), self\u2010assemble directly to form binary carrier\u2010free multi\u2010functional spherical nanoparticles (BBR\u2010HST NPs) through noncovalent bonds involving electrostatic interactions, \u03c0\u2013\u03c0 stacking, and hydrogen bonding. Because of their synergistic anti\u2010inflammatory activity, berberine\u2013hesperetin nanoparticles (BBR\u2010HST NPs) exhibit significantly better therapeutic effects on UC and inhibitory effects on inflammation than BBR and HST at the same dose by regulating the immune microenvironment and repairing the damaged intestinal barrier. Furthermore, BBR\u2010HST NPs exhibit good biocompatibility and biosafety. Thus, this study proves the potential of novel natural anti\u2010inflammatory nanoparticles as therapeutic agents for UC, which could promote the progress of drug development for UC and eventually benefit patients who suffering from it.<\/jats:p>","DOI":"10.1002\/adhm.202301826","type":"journal-article","created":{"date-parts":[[2023,9,8]],"date-time":"2023-09-08T05:47:46Z","timestamp":1694152066000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":106,"title":["Novel Natural Carrier\u2010Free Self\u2010Assembled Nanoparticles for Treatment of Ulcerative Colitis by Balancing Immune Microenvironment and Intestinal Barrier"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-7613-1766","authenticated-orcid":false,"given":"Shan","family":"Gao","sequence":"first","affiliation":[{"name":"School of Chinese Pharmacy Beijing University of Chinese Medicine  Beijing 102488 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