MOF/Polypeptide Hybrid Nanocomposites with pH/Lipase Dual Responsive Drug Release and Photodynamic Effect for Combination Treatment of Drug-Resistant Bacterial Infection

[Display omitted] •Preparation of the MOF/Polypeptide Hybrid Nanocomposites.•pH/Lipase dual responsive drug release in bacterial microenvironment.•Efficiently singlet oxygen generation under NIR irradiation.•Synergistic effect via combined chemo-photodynamic therapy against MRSA skin infection.•Excellent biocompatibility and haemo-compatibility. Multi-drug resistant (MDR) bacterial infection has become one of the most serious health issues due to its high mortality rate. To address this problem, a novel metal-organic framework (MOF)/polypeptide hybrid nanocomposite was synthesised for the combined chemo-photodynamic therapy of MDR bacterial infection. A lipase-sensitive crosslinker was used to prepare the crosslinked polypeptide outer shell of the nanocomposite, and ciprofloxacin (CIP) and methylene blue (MB) were incorporated in the zeolite imidazole framework (ZIF)/poly-γ-glutamic acid (PGA) nanocomposites to form the combined therapeutic system (ZIF/PGA-C/M) for the treatment of methicillin-resistant Staphylococcus aureus (MRSA). The ZIF/PGA-C/M displayed a negative surface charge of -11.2 mV at physiological pH, indicating improved structural stability and biocompatibility. The pH/lipase dual responsive drug release showed that up to 99.4% CIP and 76.0% MB were released at pH 5.5 in the presence of lipase from the ZIF/PGA-C/M. Moreover, the incorporated MB can effectively generate singlet oxygen (1O2) to kill the bacteria by a photodynamic effect under NIR irradiation. Remarkably, ZIF/PGA-C/M showed an efficient inhibition rate towards MRSA in both planktonic and biofilm phenotypes, and a synergistic therapeutic effect against MRSA infection in the mice model of skin infection.