Although　various　antibacterial　strategies　have　been　developed,　antibiotic　chemotherapy　remains　the　primary　clinical　treatment　for　bacterial　infections.　To　address　the　limitations　associated　with　the　traditional　antibiotic　therapy,　like　burst　drug　release,　rapid　drug　clearance,　and　the　emergence　of　drug　resistance,　it　is　highly　desirable　to　develop　drug　release　systems　that　can　realize　controlled　and　sustained　drug　release　to　enhance　the　therapeutic　efficacy.　Herein,　we　present　a　novel　drug　release　system,　CIP@SU-102,　which　shows　superior　and　long-lasting　antibacterial　activity.　CIP@SU-102　was　readily　fabricated　by　the　encapsulation　of　ciprofloxacin　(CIP),　a　cationic　broad-spectrum　antibiotic,　into　an　anionic　Zr-based　metal-organic　framework　SU-102　through　ion-exchange.　Notably,　the　loading　capacity　and　efficiency　of　CIP　were　impressively　high,　reaching　33.3%　and　66.8%,　respectively.　In　vitro　assays　demonstrated　that　CIP@SU-102　has　superior　and　prolonged　antimicrobial　activity　against　Gram-negative　(Escherichia　coli)　and　Gram-positive　(Staphylococcus　aureus)　bacteria,　including　the　methicillin-resistant　Staphylococcus　aureus　(MRSA).　Remarkably,　CIP@SU-102　could　retain　its　antibacterial　efficacy　even　after　continuous　drug　release　for　20　days.　In　vivo　assays　verified　that　CIP@SU-102　could　significantly　accelerate　infected　wound　healing　because　of　its　sustained　drug　release　properties.　Due　to　the　low　cost　and　biocompatibility　of　SU-102　as　well　as　the　affordability　of　ciprofloxacin,　CIP@SU-102　is　a　very　promising　antibacterial　agent　for　long-lasting　bacterial　disinfection　and　boosting　infected　wound　healing　in　actual　clinical　applications.　This　work　highlights　the　potential　of　the　metal-organic　framework-based　drug　release　systems　for　sustained　antimicrobial　therapy.　©　2024　The　Royal　Society　of　Chemistry.