PtCu Nano-sonosensitizers For Enhanced Sonodynamic Bacterial Elimination And Tissue Repair

The development of bacterial resistance has become a challenge for healthcare systems.Reactive oxygen species(ROS)therapy kills bacteria by inducing oxidative stress,which is effective against most microorganisms and does not involve drug resistance.Therefore,it is the most promising antibiotic replacement therapy.Currently developed ROS-based therapies include chemodynamic therapy(CDT),photodynamic therapy(PDT),sonodynamic therapy(SDT),etc.Benefiting from the non-invasive and locally limited irradiation treatment and the excellent depth of tissue penetration of ultrasound,SDT is considered a more reliable alternative therapy that can overcome the antibiotic resistance and tissue penetration limitations of traditional light-induced therapies.However,the development of highly effective sonosensitizers is still one of the main factors restricting sonodynamic therapy.Hypoxia inducible factor-1α(HIF-1α)promotes angiogenesis and thus accelerates wound healing and tissue repair,but its expression is unstable under normal oxygen conditions,limiting its usefulness.Previous studies have shown that the transition metal copper stabilizes the expression of HIF-lα,thereby accelerating the process of wound healing.Based on this,this thesis mainly focuses on the development of copper-based sonosensitizers with tissue repair function,with the intention of eradicating bacterial infection and promoting tissue repair under the action of ultrasound.The main contents include the following:1.Ultra-small platinum copper nanoparticles(PtCu NPs)were synthesized by high temperature thermal decomposition,and their physical and chemical properties were determined by a series of characterization methods.The synthesized PtCu NPs not only produced a large amount of ROS under ultrasound,but also had glutathione(GSH)consumption and Fenton-like catalytic effects.In vitro antibacterial experiments have demonstrated that SDT destroys the integrity of the bacterial membrane/wall by inducing ROS production,thus inducing bacterial death,and mouse wound models have also demonstrated that SDT can eradicate wound infection caused by Staphylococcus aureus(S.aureus).At the same time,PtCu NPs can steadily release copper ions in the physiological environment,which can stabilize HIF-1α to promote angiogenesis and accelerate wound healing.The sonosensitizer provides a new idea for the construction of multifunctional acoustic sensitizer suitable for bacterial infection and tissue repair.2.To develop the application of PtCu NPs in sonodynamic treatment of osteomyelitis.Osteomyelitis was induced by injection of S.aureus into the tibia of mice,and sonodynamic therapy was performed after local injection of PtCu NPs.Sonodynamic therapy successfully killed S.aureus at the early stage of infection,and also promoted the polarization of macrophages to accelerate tissue repair.After treatment,bone defects were completely disappeared and S.aureus was eradicated.This work provides a new strategy for the non-invasive treatment of osteomyelitis infection.In this master’s thesis,the synthetic multifunctional PtCu NPs can consume the key substances GSH and hydrogen peroxide(H2O2)in the bacterial infection environment,and produce ROS under ultrasound irradiation to induce oxidative stress and achieve high antibacterial efficiency.After bacterial removal,copper ions can continue to be released,which is conducive to tissue repair.Our work highlights a novel strategy for the effective treatment of deep bacterial infections such as osteomyelitis and tissue repair of inflammatory microenvironment regulation.