1. School of Materials Science and Engineering, Beijing University of Chemical Technology, Beijing 100029, China; 2. State Key Laboratory of Molecular Ontology, National Cancer Center/Cancer Hospital,Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100021, China; 3. Laboratory of Pharmaceutical Biotechnology, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100050, China; 4. State Key Laboratory of Metal Matrix Composites, College of Chemistry and Chemical Technology, Shanghai Jiaotong University, Shanghai 200240, China; 5. Department of Pharmacy, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100021, China; 6. Department of Biotherapy, Beijing Hospital, National Center of Gerontology, Beijing 100730, China
Abstract：OBJECTIVE The lactose-doxorubicin amphiphilic small molecule nanomicelles and evaluate its liver cancer targeting and antitumor efficacy and safety in vivo. METHODS Lactose-doxorubicin nanomicelles (Lac-DOX NMs) were prepared by thin film hydration method. The particle size was determined by dynamic light scattering and observed by transmission electron microscopy. The effect of Lac-DOX NMs on the targeting of tumor cell was investigated by cell uptake experiments.Cytotoxicity of nanomicelles and free doxorubicin were evaluated by CCK-8 assay .The subcutaneous xenograft model of BALB/c-nu mice was constructed to investigate the anti-tumor effect of Lac-DOX NMs; the effect of the preparation on liver function of mice was examined by blood biochemical test to evaluate the safety of the preparation.RESULTS Lac-DOX NMs were successfully prepared with a particle size of (169.2±0.9) nm. Cellular uptake experiments indicated that Lac-DOX NMs are targeted to HuH-7 hepatoma cells.The IC50 of nanomicelle and free DOX were 3.596 and 2.131 μg·mL-1, respectively. The results of pharmacodynamic experiments showed that Lac-DOX NMs could significantly inhibit the growth of transplanted tumors in mice. The tumor inhibition rates of high and low doses of Lac-DOX NMs were 69.72% and 52.40%, respectively, which were higher than those of free DOX (52.27%). P values are 0.000 16 and 0.94. CONCLUSION Modification of doxorubicin with lactose and its preparation into nanometer preparations can significantly improve the targeting of doxorubicin to liver cancer cells, enhance the anti-tumor effect, reduce the side effects of doxorubicin, and improve the safety of medication.
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2020, Vol. 55 
