Chinese Journal of Tissue Engineering Research ›› 2019, Vol. 23 ›› Issue (26): 4194-4199.doi: 10.3969/j.issn.2095-4344.1359

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Inhibitory effects of doxorubicin-loaded chitosan nanoparticles on osteosarcoma in mice

Li Yongheng, Cui Yan, Zhang Zhiyu
  

  1. the Fourth Affiliated Hospital of China Medical University, Shenyang 110032, Liaoning Province, China
  • Received:2019-03-16
  • Contact: Zhang Zhiyu, MD, Professor, the Fourth Affiliated Hospital of China Medical University, Shenyang 110032, Liaoning Province, China
  • About author:Li Yongheng, Master, the Fourth Affiliated Hospital of China Medical University, Shenyang 110032, Liaoning Province, China
  • Supported by:

    Liaoning Science and Technology Plan Project, No. 20170541058 (to ZZY)

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Abstract:

BACKGROUND: 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.
OBJECTIVE: To analyze the cytotoxicity of doxorubicin-loaded chitosan nanoparticles and their inhibitory effect on osteosarcoma.
METHODS: Cytotoxicity tests: Murine osteosarcoma cell line K7 was interfered with PBS containing doxorubicin-loaded chitosan nanoparticles (referred to as drug-loaded nanoparticles) and PBS containing free doxorubicin (doxorubicin concentrations 0.16, 0.31, 0.62, 1.25, 2.5, 5,10 mg/L) for 24 and 72 hours. Cell viability was measured by MTT assay. In vivo drug distribution test: Balb/c mouse (Changchun Institute of Biological Product Co., Ltd., China) models of tumor were established by subcutaneous injection of murine osteosarcoma cell line K7. When tumor volume reached 200 mm3, mice in the experimental and control groups were respectively injected with PBS containing doxorubicin-loaded nanoparticles and PBS containing free doxorubicin via the tail vein. The mice were sacrificed at 6 and 12 hours after drug administration and the fluorescence of doxorubicin in various organs was observed. In vivo tumor growth inhibition test: Balb/c mouse models of tumor were established by subcutaneous injection of murine osteosarcoma cell line K7. When tumor volume reached 50 mm3, mice in the experimental and control groups were respectively injected with PBS containing doxorubicin-loaded nanoparticles and PBS containing free doxorubicin via the tail vein. PBS was injected in the blank control group, once every 4 days, for a total of 6 times. Mouse body mass and tumor volume were daily measured. Animal experiments were approved by Animal Ethics Committee of Jilin University, China.
RESULTS AND CONCLUSION: The median lethal concentration of doxorubicin-loaded nanoparticles and free doxorubicin was 2.4 and 4.2 mg/L respectively at 24 hours after drug application, and it was 0.29 and 0.91 mg/L respectively at 72 hours after drug application. Doxorubicin-loaded nanoparticles mainly accumulated in the liver, kidney, and tumor. During the treatment period, average tumor volume in the experimental group was significantly smaller than that in the control and blank control groups (P < 0.001). The average mouse body mass in the experimental group was significantly greater than that in the control group (P < 0.001). The results show that the drug-loaded system can well control in vivo release of doxorubicin and greatly enhance the inhibitory capacity of chemotherapy drugs against osteosarcoma.

Key words: osteosarcoma, doxorubicin, chitosan, nanoparticles, polysaccharide, controlled drug release, nanosystem, tumor suppression

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