Applications Of Near Infra Red Responsive ALG-PEGDA-Gd₂O₃:Yb,Tm,Zn Composite Hydrogel In Photodynamic Antibacterial Therapy

Due to the tunable structures and properties of hydrogels and nanoparticles,nanoparticle-combined hydrogels have become a new platform for antibacterial applications,providing unprecedented opportunities to overcome the problem of antibacterial resistance.Light-responsive hydrogels have attracted much attention because of their phototunable appearance and non-invasive treatment of bacterial infections.In order to achieve minimal side effects and deep tissue penetration,near infrared light（NIR）responsive hydrogels have received increasing attention in recent years.In order to prepare NIR-responsive hydrogels,upconversion nanoparticles（UCNPs）which absorb low energy photons and emit high energy photons in the NIR region were used to prepare hydrogel-UCNPs composites.In this paper,a sodium alginate（ALG）-polyethylene glycol diacrylate（PEGDA）-Gd₂O₃:Yb,Tm,Zn（ALG-PEGDA-GUCNPs）hydrogel with NIR-responsive composite UCNPs was proposed using 980 nm NIR triggered polymerization of methacrylate groups in hydrogels.During the gelation process,under the excitation of 980 nm laser,the blue light emitted by GUCNPs was used to realize the photopolymerization of PEGDA precursor and form an interpenetrating network（IPN）with ALG.The composite hydrogel is an NIR-responsive antibacterial hydrogel that can mediate photodynamic antibacterial therapy（PDAT）.The GUCNPs were embedded in the hydrogel and acted again as a photoconverter to trigger the photochemical reaction of the photosensitive（PS）drug merocyanine 540（MC540）to generate singlet oxygen（~1O₂）to kill bacteria.This paper mainly focuses on the following aspects:1.Preparation of up-conversion fluorescent nanomaterials GUCNPs and GUCNPs-PEGDA.Using Gd（NO₃）₃,Yb（NO₃）₃,Tm（NO₃）₃,Zn（NO₃）₂ as raw materials,up-conversion fluorescent nanoparticles Gd₂O₃:Yb,Tm,Zn were synthesized by simple hydrothermal method,and the up-conversion fluorescence intensity was further improved by doping Zn²⁺into the Gd₂O₃ matrix.Taking advantage of the fluorescence properties of GUCNPs and using I784 as a photoinitiator,the in situ photopolymerization of PEGDA on GUCNPs surface was realized under the excitation of NIR light,which made GUCNPs-PEGDA have strong up-conversion fluorescence and good dispersity.In addition,the up-conversion blue fluorescence of GUCNPs and GUCNPs-PEGDA under 980 nm laser irradiation was consistent with the UV-visible absorption band of the photosensitizer MC540,so MC540 was used as PDAT drug to realize photodynamic therapy under the coordination of the two.2.Preparation and characterization of ALG-PEGDA-GUCNPs hydrogel.GUCNPs-PEGDA was used as the light source converter,and PEGDA optical crosslinking was triggered by 980 nm laser to form an interpenetrating network with ALG.The effect of PEGDA modification on the surface of GUCNPs on the porous structure,surface adhesion,swelling and degradability of the prepared composite hydrogels was investigated.3.Antibacterial properties of GUCNPs and GUCNPs-PEGDA nanoparticles.Human umbilical vein endothelial cells（HUVEC）and mouse fibroblasts（L929）were used as cell models for cytotoxicity evaluation,and Escherichia coli（E.coli）and Staphylococcus aureus（S.aureus）were used as in vitro antibacterial properties bacterial models for research.The effects of surface PEGDA modification on the cytotoxicity and antibacterial activity of GUCNPs were compared.It was found that GUCNPs-PEGDA coated by PEGDA with core-shell structure had lower cytotoxicity than GUCNPs.Photodynamic antimicrobial therapy mediated by upconversion fluorescent nanomaterials showed excellent antibacterial activity in vitro.Moreover,it had a strong digestion effect on the bacterial biofilm.After photodynamic therapy,the quality of the bacterial biofilm was significantly reduced and the biofilm was greatly destroyed,showing excellent broad-spectrum antibacterial activity and non-selective effect,which can further reduce the risk of drug resistance.4.Study on antibacterial properties of ALG-PEGDA-GUCNPs hydrogel.E.coli and S.aureus were used as bacterial models to study their antibacterial performance in vitro and in vivo.The biocompatibility and antibacterial activity of ALG-PEGDA-GUCNPs hydrogel in vitro and in vivo were investigated.ALG-PEGDA-GUCNPs composite hydrogels with NIR response showed excellent photodynamic antibacterial effect in vivo and in vitro.ROS storms generated during the photodynamic process can kill bacteria.