Dual Stimuli-Responsive smart fibrous membranes for efficient Photothermal/Photodynamic/Chemo-Therapy of Drug-Resistant bacterial infection

Abstract

• A dual stimuli-responsive CIZPP smart antibacterial membrane was investigated. • CIZPP exhibited enhanced photothermal stability and singlet oxygen generation. • CIZPP endowed NIR/pH stimuli-responsive delivery of curcumin. • CIZPP showed desirable biocompatibility and potent antibacterial activity. • CIZPP contributed to rapid recovery rate of MRSA infected wound sites. It remains great challenges to place temporal and spatial control over delivering of antibacterial agents in biomaterials and tissue engineering research. Besides, the physically mixed photosensitizers of indocyanine green (ICG) usually suffer from thermal/photo instability and leakage that restrict the photophysical chemistry bactericidal processes. In this work, to overcome the limitations, the phytochemical curcumin (Cur) and ICG were successfully coencapsulated into the zeolitic imidazolate framework-8/polylactic acid (ZIF-8/PLA) electrospun fibrous membrane nanocarriers, which were further coated with phase-change material (PCM) through noncovalent interactions. The obtained Cur-ICG@ZIF-8/PLA/PCM (CIZPP) composites exhibit desirable biocompatibility and potent antibacterial activity through photothermal/photodynamic/chemo-killing effects. Dual stimuli-responsive (NIR and pH) release of curcumin from CIZPP was achieved by NIR induced phase change mechanism of the PCM, in conjunction with dissociating of ZIF-8 in bacterial infection acidic microenvironment. Meanwhile, CIZPP exhibits enhanced photothermal stability and singlet oxygen ( 1 O 2 ) generation than that of ICG immediately absorbed on PLA/PCM scaffolds due to the confinement effect. In vitro and in vivo experimental evidences demonstrate CIZPP could restrain drug-resistant bacterial infection through irreversibly damage on the cell membrane. Compared with traditional stimuli-responsive electrospun fibrous membranes, CIZPP shows multiple responsiveness, efficient and rapid antibacterial performance with bactericidal rates of more than 99%, contributing to rapid recovery rate of infected wound sites with minimal biological burden. This work provides a competitive strategy for developing stimuli-responsive smart platform to treat bacterial induced wound infection.