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Increased macrophage infiltrate in parallel with microglial activation and MMP9 overexpression on CNV lesions is shown to contribute to the inflammatory process and then enhance pathological ocular angiogenesis. Graphene oxide quantum dots (GOQDs), as natural antioxidants, exert anti\u2010inflammatory effects and minocycline is a specific macrophage\/microglial inhibitor that can suppress both macrophage\/microglial activation and MMP9 activity. Herein, an MMP9\u2010responsive GOQD\u2010based minocycline\u2010loaded nano\u2010in\u2010micro drug delivery system (C18PGM) is developed by chemically bonding GOQDs to an octadecyl\u2010modified peptide sequence (C18\u2010GVFHQTVS, C18P) that can be specifically cleaved by MMP9. Using a laser\u2010induced CNV mouse model, the prepared C18PGM shows significant MMP9 inhibitory activity and anti\u2010inflammatory action followed by antiangiogenic effects. Moreover, C18PGM combined with antivascular endothelial growth factor antibody bevacizumab markedly increases the antiangiogenesis effect by interfering with the \u201cinflammation\u2010MMP9\u2010angiogenesis\u201d cascade. The prepared C18PGM shows a good safety profile and no obvious ophthalmic or systemic side effects. The results taken together suggest that C18PGM is an effective and novel strategy for combinatorial therapy of CNV.<\/jats:p>","DOI":"10.1002\/smll.202207335","type":"journal-article","created":{"date-parts":[[2023,3,5]],"date-time":"2023-03-05T06:10:37Z","timestamp":1677996637000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["MMP9\u2010Responsive Graphene Oxide Quantum Dot\u2010Based Nano\u2010in\u2010Micro Drug Delivery System for Combinatorial Therapy of Choroidal Neovascularization"],"prefix":"10.1002","volume":"19","author":[{"given":"Keke","family":"Huang","sequence":"first","affiliation":[{"name":"Institute of Advanced Materials for Nano\u2010Bio Applications School of Ophthalmology and Optometry Eye Hospital Wenzhou Medical University  Wenzhou Zhejiang 325027 P. R. 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