Inhibitory effects of hyaluronic acid nanoparticles loading doxorubicin and cisplatin on allograft breast cancer in mice / 吉林大学学报(医学版)

ABSTRACT

Objective:To investigate the application of CD44 receptor-targeted nanoparticles HACDDP-DOX in the treatment of breast cancer, and to clarify its inhibitory effect on allograft breast cancer in the mice. Methods:Hyaluronic acid(HA)was used to construct a breast cancer targeted nanoparticle via green synthesis approach,and its particle size,stability and doxorubicin release profile at different pH conditions were measured. Then the breast cancer models were constructed by inoculating 4T1 cells into the mouse mammary fat pad.The model mice were randomly divided into control group,DOX/CDDP group and HACDDP-DOX group according to the tumor volumes and the body weights.PBS,free drug DOX/CDDP and HACDDP-DOX were intravenously injected into the allograft breast cancer models on the 1st,5th and 9th days after the tumor volume reached about 80 mm3. The antitumor effect and biosafety of HACDDP-DOX were evaluated by detecting the tumor volume,mouse weight and immunohistopathology.Moreover,the biological distribution of HACDDP-DOX in the mice was studied by biofluorescence imaging.Results:The average particle size of HACDDP-DOX was(80.0 ± 17.4)nm,which was stable under pH 7.4.Under acidic condition,the particle size was increased and the DOX was effectively released. Compared with DOX/CDDP group,the body weight of the mice in HACDDP-DOX group was increased(P<0.05) and the tumor volume was decreased(P<0.05).The HE staining results showed that the liver of the mice in control group had tumor metastasis and the alveolar septum was widened.The tumor tissue of the mice in DOX/CDDP group and HACDDP-DOX group were all necrotic,while in HACDDP-DOX group the degree of necrosis was significantly higher than DOX/CDDP group.Compared with DOX/CDDP group,the activity of Caspase-3 in HACDDP-DOX group was significantly increased(P<0.01),while the Ki-67 activity was significantly decreased (P<0.01).The biofluorescence imaging showed that the nanoparticle HACDDP-DOX could accumulate to the tumor site by targeting,and effectively release the drug.Conclusion:HACDDP-DOX nanoparticles can effectively target the breast cancer cells,reduce the toxicity of chemotherapy drugs,and enhance the therapeutic effect of breast cancer.