Investigation On Oxygenated Drug Delivery System Based On Fluorinated Chitosan

Objective : Sonodynamic therapy(SDT)uses a combination of sonosensitizers and ultrasound(US)to damage tumor cells and tissues,so as to achieve the purpose of treating cancer.At present,this method has become an important method for clinical treatment of cancer.General sonosensitizers lack tumor targeting,and the hypoxic microenvironment inside the tumor limits the effect of SDT.Therefore,there is an urgent need for SDT therapy to increase the accumulation concentration of sonosensitizers at the tumor site and improve local tumor hypoxia.This project intends to design,synthesize and verify a nanoparticle that can improve the absorption of sonosensitizers and increase oxygenation in tumors.Methods : Fluorinated chitosan(FCS)and catalase(CAT-TPP)modified with triphenylphosphine(TPP)were synthesized by amide reaction.Afterwards,the CAT-TPP/FCS@Ce6 drug delivery system was constructed using Chlorin e6(Ce6)as a model drug,because it contains biological macromolecule cat,so it can catalyze the high concentration of hydrogen peroxide inside the tumor to continuously produce oxygen,improves the tumor’s hypoxic environment,and achieves the dual effects of targeting and oxygenation.Verify its oxygenation and SDT efficacy in liver cancer cell models;verify its ability to target absorption and its inhibitory effects on tumors through in vivo models.Results:FT-IR and NMR results indicate the successful preparation of FCS,and UV-Vis indicates the successful modification of CAT-TPP.According to the TEM characterization,CAT-TPP/FCS@Ce6 are spherical nanoparticles with a particle size of about 140 nm.The MTT experiment shows that CAT-TPP/FCS has good biological safety.Cell experiment results show that CAT-TPP/FCS@Ce6 can be well taken up by tumor cells,and can escape from lysosomes to target mitochondria.By measuring the yield of reactive oxygen species(ROS),the oxygenation ability of CAT-TPP/FCS@Ce6 in hypoxic tumor environment was verified.In vivo anti-tumor experiments show that CAT-TPP/FCS@Ce6 can significantly inhibit tumor growth under the action of ultrasound radiation.Conclusions : In this study,a CAT-TPP/FCS@Ce6 drug delivery system was successfully prepared,and CAT-TPP/FCS@Ce6 can effectively accumulate in tumor tissues,and can significantly inhibit tumor growth under the action of ultrasound radiation,which has a wide range of applications prospect.