Application Exploration Of Photothermal Therapy Based On Good Biocompatible Nanomaterials For Diabetic Wound Infection

Objctive:Infection is one of the most common and serious complications for diabetic foot ulcers.Antibiotics application is the main method.However,diabetic vascular stenosis restricts transportation of antibiotics,the importance is that emergence of multi-drug resistant strains makes efficacy of antibiotics worser.Clinical treatment of diabetic foot infection has fallen into a great dilemma.Nanotechnology provides a new method for its treatment.Photothermal therapy is a new non-antibiotic method that uses photothermal reagents to convert light into heat to kill targets.So,this study intends to use biocompatible inorganic nanomaterials BSA-Cu S and organic nanomaterials PDA as ideal reagents for photothermal treatment and in order to provide a new treatment for diabetic wound infection.Materials and Method:1.Preparation and characterization of BSA-CuS and PDA: BSA-CuS and PDA were synthesized by simple chemical reaction and characterized by electron microscopy,infrared and ultraviolet instruments.2.In vitro cytotoxicity: MTT assay was used to evaluate the cytotoxicity.3.In vitro photothermal antibacterial experiment: The experiment was divided into four groups:(1)bacteria+PBS;(2)bacteria+BSA-Cu S/PDA;(3)bacteria+PBS+laser;(4)bacteria+BSA-Cu S/PDA+laser,and the number of bacterial surviving colonies was observed to evaluate in vitro antibacterial effect of PTT based on BSA-Cu S/PDA.4.In vivo toxicity: Changes of blood biochemical parameters of liver and kidney(total protein,albumin,globulin,alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase,gamma-glutamyltransferase,creatinine,uric acid),vital organ tissues(heart,liver,spleen,lung and kidney)and daily body weight of mice treated with BSA-Cu S/PDA or PBS to examine in vivo toxicity of BSA-Cu S and PDA.5.In vivo photothermal antibacterial experiment: establish mice model of diabetic infected wound.The experiment was divided into four groups:(1)nondiabetic infected mice with no treatment;(2)diabetic infected mice with no treatment;(3)diabetic infected mice were treated with PBS+laser;(4)diabetic infected mice were treated with BSA-Cu S/PDA+laser;(5)diabetic infected mice were treated with oral amoxicillin.The changes of wounds were observed to evaluate in vivo antibacterial effect of PTT based on BSA-Cu S/PDA.Results:1.Preparation and characterization of BSA-Cu S and PDA: BSA-Cu S and PDA were synthesized by simple chemical methods.They were small-sized nanomaterials suitable for living,had strong near-infrared absorption and photothermal capacity.2.In vitro cytotoxicity: The survival rate of cells after co-culture with BSA-Cu S/ PDA was still high,which confirmed that BSA-Cu S and PDA had low cytotoxicity.3.In vitro photothermal antibacterial experiment: After BSA-Cu S/PDA and laser irradiation,most of the bacteria were killed,which proved that PTT based on BSA-Cu S/PDA had strong in vitro photothermal antibacterial ability,BSA-Cu S/PDA or laser irradiation alone was difficult to exert a strong antibacterial effect.4.In vivo toxicity: There were no significant changes in blood biochemical parameters of liver and kidney,no obvious pathological changes in H&E staining of important organ tissuesand no significant changes in weight of two groups treated with BSA-Cu S/PDA and PBS,demonstrating that both BSA-Cu S and PDA had lower in vivo toxicity.5.In vivo photothermal antibacterial experiment: PTT based on BSA-Cu S/PDA showed high effective antibacterial treatment effect without obvious damage to surrounding tissues.And better than the laser and oral antibiotic treatment effects.Conclusion:BSA-Cu S and PDA were synthesized by simple processes.They were small-sized nanomaterials suitable for living,and had low toxicity,good biocompatibility and high photothermal conversion.A powerful photothermal antibacterial effect on diabetic infected wound was achieved.This study was directly targeted to kill pathogens without drawbacks of antibiotic methods,which provided a new strategy and theoretical basis for the treatment of diabetic wound infection.