Bo Lian1, Hua Wei2, Ruiyan Pan3, Jingui Sun4, Bo Zhang3, Jingliang Wu1, Xiujie Li1, Guixiang Tian1. 1. School of Bioscience and Technology, Weifang Medical University, Weifang 261053, People's Republic of China. 2. Department of Endocrinology, ShouGuang Peoples' Hospital, Weifang 262700, People's Republic of China. 3. School of Pharmacy, Weifang Medical University, Weifang 261053, People's Republic of China. 4. Department of Oncology, ShouGuang Peoples' Hospital, Weifang 262700, People's Republic of China.
Abstract
BACKGROUND: Tumor angiogenesis plays a crucial role in tumor development, and recent efforts have been focused on combining proapoptotic and antiangiogenic activities to enhance antitumor therapy. METHODS: In this study, galactose-modified liposomes (Gal-LPs) were prepared for co-delivery of doxorubicin (DOX) and combretastatin A4 phosphate (CA4P). The co-cultured system composed of BEL-7402 and human umbilical vein endothelial cells (HUVEC) cells was established to effectively evaluate in vitro anti-tumor activity through cell viability and cell migration assay. Furthermore, both in vivo bio-distribution and anti-hepatoma effect of DOX&CA4P/Gal-LPs were investigated on H22 tumor cell-bearing mice. RESULTS: The results showed that DOX&CA4P/Gal-LPs were spherical with a mean particle size of 143 nm, and could readily be taken up by BEL-7402 cells. Compared with a mixture of free DOX and CA4P, the DOX&CA4P/Gal-LPs were more effective in inhibiting cell migration and exhibited stronger cytotoxicity against BEL-7402 cells alone or a co-cultured system. The in vitro studies showed that the co-cultured system was a more effective model to evaluate the anti-tumor activity of combination therapy. Moreover, DOX&CA4P/Gal-LPs exhibited a greater anti-hepatoma effect than other drug formulations, indicating that Gal-LPs could promote drug accumulation in the tumor region and improve the anti-tumor activity. CONCLUSION: Gal-LPs co-loaded with chemotherapeutic and antiangiogenic drugs are a promising strategy for anti-hepatoma therapy.
BACKGROUND: Tumor angiogenesis plays a crucial role in tumor development, and recent efforts have been focused on combining proapoptotic and antiangiogenic activities to enhance antitumor therapy. METHODS: In this study, galactose-modified liposomes (Gal-LPs) were prepared for co-delivery of doxorubicin (DOX) and combretastatin A4 phosphate (CA4P). The co-cultured system composed of BEL-7402 and human umbilical vein endothelial cells (HUVEC) cells was established to effectively evaluate in vitro anti-tumor activity through cell viability and cell migration assay. Furthermore, both in vivo bio-distribution and anti-hepatoma effect of DOX&CA4P/Gal-LPs were investigated on H22 tumor cell-bearing mice. RESULTS: The results showed that DOX&CA4P/Gal-LPs were spherical with a mean particle size of 143 nm, and could readily be taken up by BEL-7402 cells. Compared with a mixture of free DOX and CA4P, the DOX&CA4P/Gal-LPs were more effective in inhibiting cell migration and exhibited stronger cytotoxicity against BEL-7402 cells alone or a co-cultured system. The in vitro studies showed that the co-cultured system was a more effective model to evaluate the anti-tumor activity of combination therapy. Moreover, DOX&CA4P/Gal-LPs exhibited a greater anti-hepatoma effect than other drug formulations, indicating that Gal-LPs could promote drug accumulation in the tumor region and improve the anti-tumor activity. CONCLUSION: Gal-LPs co-loaded with chemotherapeutic and antiangiogenic drugs are a promising strategy for anti-hepatoma therapy.