Biofilm Microenvironment-responsive Molybdenum Disulfide Nanocarriers And Phototherapy For Synergistic Anti-drug-resistant Bacteria And Wound Healing

Drug-resistant bacterial infections pose a serious threat to human health.The formation of biofilm is one of the main factors for the development of drug resistance in bacteria with a microenvironment characterized by lack of oxygen,microacid and high glutathione.Wounds infected by drug-resistant bacteria are difficult to heal,traditional treatments such as antibiotics have little effect,and nanomaterial-based photothermal therapy（PTT）,photodynamic therapy（PDT）,and sonodynamic therapy（SDT）have become research hotspots for antimicrobial therapy.Due to the emergence of bacterial resistance and the protection of recalcitrant biofilms,single antimicrobial strategies such as PTT and PDT do not meet the need for long-term antibacterial work,and combined phototherapy to inhibit drug-resistant bacterial infections has shown synergistically enhanced antimicrobial activity and received widespread attention.In this thesis,molybdenum disulfide（MoS₂）nanospheres with high photothermal conversion efficiency were used as the core to construct pH and near-infrared light dual-responsive PTT/PDT synergistic therapy-derived antimicrobial nanocarriers for in vivo/in vitro antibacterial activity and mechanism studies to investigate the therapeutic effects of these MoS₂nanocarriers against drug-resistant bacterial infections and promote wound healing.The study contents and results are as follows.（1）MoS₂nanospheres（120-150 nm）were synthesized by hydrothermal method,positively charged quaternary ammonium salts（QAS）were grafted on the surface with MoS₂nanospheres and combined with the photosensitizer dihydroporphyrin e6（Ce6）and the active ingredient of Chinese medicine,Panax notoginseng saponin（PNS）,and finally the above materials were wrapped with acid-sensitive zeolite imidazole ester backbone material（ZIF-8）.ZIF-8 in biofilm The acidic interpretation of the released material under micro-acidic environment,the positively charged quaternized polyethyleneimine（QPEI）adsorbed on the negatively charged bacterial cell membrane surface,and the long carbon chain on QPEI inserted into the cell membrane to make the cell lysis and intracellular oxygen release to relieve the periplasmic hypoxia.Using near-infrared light irradiation,MoS₂generates photothermal and synergistic antibacterial effects with Ce6-excited reactive oxygen species（ROS）,while using PNS with auxiliary antibacterial and wound healing efficacy for treatment.The results showed that the nanomaterial（MQCP@ZIF-8）has a photothermal conversion efficiency of 56%,and the inhibition rate of both drug-resistant Escherichia coli（E.coli）and drug-resistant Staphylococcus aureus（S.aureus）exceeds 95%,and is biosafe and can effectively promote wound healing.Experiments such as transcriptome analysis revealed the mechanism of bacterial inhibition by nanocarriers,including promoting biofilm ablation,disrupting cell membranes and affecting intracellular material and energy metabolism.（2）In order to further optimize the antibacterial efficiency and wound healing performance of nanocarriers,combined PTT/PDT/gaseous signaling agent antibacterial nanocarriers were designed.Firstly,the MoS₂preparation process was improved to prepare smaller size MoS₂nanospheres（90-110 nm）on the surface of which sodium nitroalginate（SANO）and Ce6 were attached and wrapped with calcium carbonate（Ca CO₃）spherulite.Ca²⁺release is pH-sensitive,can passively target the bacterial biofilm,and can act as a coagulation factor to promote wound healing.Photothermal warming was induced by NIR excitation to promote the release of Ce6,which led to the production of active nitric oxide（NO）by SANO and the synergistic release of ROS and NO.The results showed that the nanocarrier（MSC@Ca CO₃）had a photothermal conversion efficiency of 48.9%,inhibited drug-resistant E.coli and drug-resistant S.aureus by more than 96%,excellent in vivo antibacterial and wound healing effects,and had good biocompatibility.In summary,the nanoantibacterial carriers designed in this thesis can effectively inhibit biofilm growth and resist drug-resistant bacterial infections,with good antibacterial and wound healing promoting activities,and also exhibit anti-tumor and post-operative repair potential for tumor treatment,with good clinical application prospects.The related research results can provide a reference for the development and application of PTT/PDT multifunctional antibacterial carriers and provide data support for the in-depth study of the molecular mechanism of resistance to drug-resistant bacteria in novel combination therapies.