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Jihui Lu, Zhijia Wang, Desheng Cai, Xiaoyu Lin, Xuemei Huang, Zhihua Yuan, Yaozhi Zhang, Haimin Lei, Penglong Wang School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing, 102488, People’s Republic of ChinaCorrespondence: Penglong Wang, School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing, 102488, People’s Republic of China, Email wpl581@126.com Haimin Lei, School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing, 102488, People’s Republic of China, Email hm_lei@126.comBackground: Deaths from bacterial infections have risen year by year. This trend is further aggravated as the overuse antibiotics and the bacterial resistance to all known antibacterial agents. Therefore, new therapeutic alternatives are urgently needed.Methods: Enlightenment the combination usage of traditional herb medicine, one carrier-free binary nanoparticles (GA-BBR NPs) was discovered, which was self-assembled from gallic acid and berberine through electrostatic interaction, π-π stacking and hydrophobic interaction; and it could be successfully prepared by a green, cost-effective and “one-pot” preparation process.Results: The nanoparticles exhibited strong antibacterial activity and biofilm removal ability against multidrug-resistant S. aureus (MRSA) by downregulating mRNA expression of rpsF, rplC, rplN, rplX, rpsC, rpmC and rpsH to block bacterial translation mechanisms in vitro and in vivo, and it had well anti-inflammatory activity and a promising role in promoting angiogenesis to accelerate the wound healing on MRSA-infected wounds model in vivo. Additionally, the nanoparticles displayed well biocompatibility without cytotoxicity, hemolytic activity, and tissue or organ toxicity.Conclusion: GA-BBR NPs originated from the drug combination has potential clinical transformation value, and this study provides a new idea for the design of carrier-free nanomedicine derived from natural herbals.Graphical Abstract: Keywords: carrier-free binary self-assemblies, natural herbal ingredients, antibacterial, wound healing, anti-inflammatory, angiogenesis |