Leiqiang Han1, Tianqi Wang1, Shengjun Mu1, Xiaolan Yin1, Shuang Liang1, Hao Fang2, Yongjun Liu1, Na Zhang1. 1. Department of Pharmaceutics, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 Wenhua Xi Road, Jinan 250012, Shandong, China. 2. Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 Wenhua Xi Road, Jinan 250012, Shandong, China.
Abstract
AIM: To optimize the synergistic efficacy of combination therapy with controlled molar ratio, complex small molecule-based nanodrug (Co-SMND) of 5-fluorouracil (5-Fu)/vorinostat (SAHA) was developed. MATERIALS & METHODS: Co-SMND with various ratios of 5-Fu-D-α-tocopherol (VE)/SAHA-VE were prepared and characterized including co-assembly mechanism, hydrolytic stability, cytotoxicity, synergistic effect and apoptosis inducing ability. The antitumor activity, systematic toxicity and biodistribution of optimized Co-SMND were evaluated in CT-26 bearing BALB/c mouse. RESULTS: Maximal synergistic effect of Co-SMND could be obtained via simply adjusting the feeding molar ratio. The optimized Co-SMND showed superior in vivo antitumor efficacy, upregulated security and selective intratumoral accumulation. CONCLUSION: Such Co-SMND is of great significance for future clinical translation, and would be an efficient platform for combination chemotherapy.
AIM: To optimize the synergistic efficacy of combination therapy with controlled molar ratio, complex small molecule-based nanodrug (Co-SMND) of 5-fluorouracil (5-Fu)/vorinostat (SAHA) was developed. MATERIALS & METHODS:Co-SMND with various ratios of 5-Fu-D-α-tocopherol (VE)/SAHA-VE were prepared and characterized including co-assembly mechanism, hydrolytic stability, cytotoxicity, synergistic effect and apoptosis inducing ability. The antitumor activity, systematic toxicity and biodistribution of optimized Co-SMND were evaluated in CT-26 bearing BALB/c mouse. RESULTS: Maximal synergistic effect of Co-SMND could be obtained via simply adjusting the feeding molar ratio. The optimized Co-SMND showed superior in vivo antitumor efficacy, upregulated security and selective intratumoral accumulation. CONCLUSION: Such Co-SMND is of great significance for future clinical translation, and would be an efficient platform for combination chemotherapy.
Entities:
Keywords:
5-fluorouracil; combination therapy; nanodrug; ratio adjustable; self-assemble; vorinostat