BODIPY-and Porphyrin-Based Photosensitizers For Photodynamic Inactivation Of Bacteria

Since the discovery of penicillin in 1928,antibiotics play an irreplaceable role in the fields of human industrial and agricultural production and medical health.However,the abuse and misuse of antibiotics has resulted in"superbug",accelerate the antibiotic resistance crisis in the global medical and health field.The rise in antibiotic resistance has drawn great interest in the research and development of alternative antimicrobials with high antibacterial activity and low likelihood of generating bacterial resistance.A number of alternative antimicrobial materials/techniques have been proposed to treat bacterial infections,such as antibacterial peptides,quaternary ammonium compounds,metal nanostructures,photothermal therapy,antimicrobial photodynamic therapy?APDT?,etc.APDT is a promising new type of antibacterial method.APDT involves the use of photosensitizers,visible or near-infrared light,and molecular oxygen to generate reactive oxygen species?ROS?.ROS can damage membrane lipids,proteins,and DNA of cells,and ultimately cause cell death.Due to the unique antibacterial mechanism,APDT can minimize the development of bacterial resistance.Photosensitizer is one of the important factors affecting the antibacterial effect of APDT.Generally speaking,photosensitizers contain hydrophobic conjugated groups and need to introduce appropriate functional groups through chemical modification to improve their water solubility and dispersibility.Therefore,designing and synthesizing photosensitizers with high ROS yield and hydrophilic is essential for APDT.Based on the above research objectives,two photosensitizers were synthesized in this thesis.Firstly,BODIPY derivatives are well-known fluorescent probes with high photochemical stability and fluorescence quantum yields.Maltoheptaose have abundant hydroxyl groups,exhibits hydrophilic and biocompatible features.In this work,a maltoheptaose-decorated BODIPY photosensitizer?BODIPY-Mal-I?was synthesized via copper?I?-catalyzed azide alkyne cycloaddition?CuAAC?reaction,followed by diiodo substitution at 2,6-positions of BODIPY core.BODIPY-Mal-I consists of a hydrophobic BODIPY unit and a hydrophilic maltoheptaose segment.It self-assembles in an aqueous medium and forms microaggregates.The as-obtained BODIPY-Mal-I show enhanced singlet oxygen generation efficacy,in comparison to halogen-free BODIPY derivative?BODIPY-Mal?.BODIPY-Mal-I can generate reactive oxygen species?ROS?under the irradiation of visible light?400–780 nm?,it exhibit antibacterial properties,while it can kill Gram-positive bacteria efficiently in both planktonic forms and biofilms.In addition,BODIPY-Mal-I shows low cytotoxicity towards zebrafish embryo without light shining.These results indicate that BODIPY-Mal-I with strong bacterial killing and biofilm eradication abilities as well as low biological toxicity could serve as an efficient photosensitizer for antibacterial PDT of bacterial infections.Secondly,Porphyrins are well known aromatic macrocyclic compounds and have long wavelength absorption in the visible region of the electromagnetic spectrum.The unique photophysical and photochemical properties of porphyrins make them promising for photosensitizer?PS?in antimicrobial PDT.Poly?L-lysine?exhibits positive charge under physiological p H,and has a broad spectrum of antibacterial activity against common pathogens.Porphyrin derivative?TPP-OH?was functionalized with Poly?L-lysine??PLL?via Cu AAC reaction,the PLL-decorated porphyrin derivative?TPP-PLL?was successfully synthesized.TPP-PLL can eradicate the common pathogens.Under 635 nm laser irradiation,TPP-PLL generates ¹O₂ and shows synergistic antimicrobial effect on the Gram-positive bacteria.TPP-PLL exhibits high hemocompatibility in the hemolysis assay and good selectivity for the common pathogens over red blood cells.In addition,the interactions between TPP-PLL and bacteria can be used to identify the Gram-positive bacteria through observing their sedimentation behavior and the color of the co-cultured bacteria cakes.Thus,the PLL-decorated porphyrin derivative can serve as a promising PS for the photodynamic inactivation of Gram-positive bacteria,and show high potential in the bacteria identification.