Ultrasmall WO_3-x@?-poly-L-glutamic Acid Nanoparticles As A Photoacoustic Imaging And Effective Photothermal-Enhanced Chemodynamic Therapy Agent For Cancer

Chemodynamic therapy is a treatment method that uses hydroxyl radical(·OH)generated by Fenton reaction or Fenton-like reaction in situ to kill tumor cells.It has only endogenous substance activation and high regioselectivity.The advantage is an emerging and thriving in situ cancer treatment strategy.Chemodynamic therapy(CDT)is an emerging and vigorous in situ cancer treatment method that kills tumor cells by generating a high activity ·OH by hydrogen peroxide at the tumor site by Fenton reaction or Fenton-like reaction.It has the advantages of only activation by endogenous substances and high regioselectivity.However,the therapeutic effects of CDT are hindered by low Fenton-like reaction speeds in cells.The synergistic treatment strategy of cancer can use different treatment methods to cooperate with each other and complement each other to achieve better anticancer effect by using low doses of therapeutic drugs and avoid side effects caused by high doses.Based on the principle that high temperature can increase the reaction rate,we propose a photothermal-enhanced chemodynamic therapy strategy.details as follows:Part one,the synthesis and characterization of ?-poly-L-glutamic acid-coated non-stoichiometric tungsten oxide nanoparticles(WO3-x@?-PGA NPs).First,we use WCl6 as the tungsten source to synthesize WO3-x@?-PGA NPs with size of 5.75 ± 0.93 nm and excellent water solubility and biocompatibility by solvothermal method,The photothermal conversion efficiency of the nanoparticle is as high as 25.8%,and the highest temperature is not significantly decreased after 6 times of photothermal cycle,and the in vitro photoacoustic and chemodynamic performance are excellent.Part two,WO3-x@?-PGA NPs are used for photothermal-enhanced chemodynamic therapy.Firstly,the nanoparticles were proved to have good biocompatibility by MTT analysis and hemolysis experiments.Subsequently,using the small animal photoacoustic imaging system and histological distribution method,the transplanted mouse breast cancer tumor was used as a model to determine the maximum accumulation of WO3-x@?-PGA NPs at the tumor site 4 h after the intravenous injection.Based on the above-mentioned maximum enrichment of tumors,photothermal-enhanced chemodynamic therapy was performed on a mouse model of breast cancer.H&E staining,TUNEL detection and 18-day follow-up observations demonstrate that the photothermal-enhanced chemodynamic therapy strategy based on WO3-x@?-PGA NPs has a good therapeutic effect and can effectively cure transplanted mouse breast cancer tumors.Through the research of this thesis,we provide a new nanoparticles for the diagnosis and therapy of tumors,and also confirmed that hotothermal-enhanced chemodynamic therapy is an effective synergistic therapy strategy,further promoting the development of chemodynamic therapy.