Inhibitory Effects Of Chitosan Nanoparticles Loading With Doxorubicin On Osteosarcoma In Mice

Objective: A large number of recent studies have shown that the nanocarrier system can achieve drug release or activation in tumor tissues,increase local drug concentration,reduce drug accumulation in normal tissues,and reduce adverse reactions.Thus,to analyze the cytotoxicity of chitosan nanoparticles loaded with doxorubicin and its inhibitory effect on osteosarcoma.Methods:(1)Cytotoxicity assay: Intervention of murine osteosarcoma cell line K7 with PBS containing chitosan nanoparticles loaded with doxorubicin(referred to as drug-loaded nanoparticles)and PBS containing free doxorubicin(all 7 were set)Concentration),after 24,72 h intervention,cell viability was measured by MTT assay.(2)In vivo drug distribution test: a mouse model of Balb/c mice was established by subcutaneous injection of mouse osteosarcoma cell line K7.When the tumor volume reached 200 mm3,the experimental group and the control group were injected with PBS containing drug-loaded nanoparticles and containing free Doxorubicin in PBS;mice were sacrificed at 6,12 h after injection to observe the fluorescence of doxorubicin in various organs.(3)In vivo anti-tumor test: The mouse model of Balb/c mice was established by subcutaneous injection of mouse osteosarcoma cell line K7.When the tumor volume reached 50 mm3,the experimental group and the control group were injected with PBS containing drug-loaded nanoparticles and PBS containing free doxorubicin respectively.The blank group was injected with PBS and injected once every 4 days for 6 times.The body mass and tumor volume of the mice were measured every day.Results :(1)When the drug was applied for 24 h,The median lethality of drug-loaded nanoparticles and free doxorubicin in killing osteosarcoma cells was 2.4,4.2 mg/L;72 h,the median lethality of drug-loaded nanoparticles and free doxorubicin in killing osteosarcoma cells The mass concentrations were 0.29 and 0.91 mg/L,respectively.(2)Nanoparticles are mainly concentrated in the liver,kidney and tumor.(3)During the treatment period,the average tumor volume of the experimental group was obviously smaller than that of the control group and the blank group(P < 0.001),and the average body mass of the experimental group was greater than that of the control group(P < 0.001).Conclusions:The results show that the drug-loading system can well achieve the in vitro and in vivo controlled release of doxorubicin,and significantly improve the inhibitory ability of chemotherapy drugs on osteosarcoma.