Shi Xiaoxin, He Dongxiu, Tang Guotao, Tang Qian, Xiong Runde, Ouyang Hu, Yu Cui-Yun
Institute of Pharmacy & Pharmacology, University of South China Hengyang Hunan China
Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study Hengyang Hunan China
RSC Adv. 2018 May 29;8(35):19868-19878. doi: 10.1039/c8ra01025k. eCollection 2018 May 25.
In the present study, we covalently coupled folic acid (FA) and 5-fluorouracil acetic acid (FUA) on the surface of quantum dots (QDs) to produce a tumor targeting drug delivery system, FA-QDs-FUA. The QDs not only act as hepatocellular carcinoma (HCC)-targeted delivery vehicles, but also play a key role in imaging. The structural and optical properties of as-prepared FA-QDs-FUA were characterized using UV-visible spectra, fluorescence spectra, infrared spectra, particle size and zeta potential. hemolysis activity, cytotoxicity and targeting specificity of the FA-QDs-FUA system were also evaluated. The anti-tumor efficacy of FA-QDs-FUA in tumor-bearing mice was investigated. The average particle size and zeta potential of FA-QDs-FUA was 220.28 nm and -13.3 mV, respectively. The drug-loading content of FA-QDs-FUA was 36.85% ± 1.61% ( = 3). The release profile of 5-FU from FA-QDs-FUA demonstrated a slow and sustained release behaviour as compared to free 5-FU drug. The results of the cellular experiment demonstrated that FA-QDs-FUA reduced cytotoxicity as compared to free 5-FU and targeted more easily hepatocellular carcinoma cells (SMMC-7721 and HepG2) than normal cells. Mice treated with FA-QDs-FUA showed superior tumor suppression compared to those treated with free 5-FU at 4.72 mg kg of 5-FU. Therefore, the FA-QDs-FUA system can be used as a promising candidate for improving 5-FU efficacy and tumor targeting specificity with limited toxicity.
在本研究中，我们将叶酸（FA）和5-氟尿嘧啶乙酸（FUA）共价偶联到量子点（QD）表面，以制备一种肿瘤靶向给药系统，即FA-QDs-FUA。量子点不仅作为肝细胞癌（HCC）靶向递送载体，还在成像中起关键作用。使用紫外可见光谱、荧光光谱、红外光谱、粒径和zeta电位对所制备的FA-QDs-FUA的结构和光学性质进行了表征。还评估了FA-QDs-FUA系统的溶血活性、细胞毒性和靶向特异性。研究了FA-QDs-FUA在荷瘤小鼠中的抗肿瘤疗效。FA-QDs-FUA的平均粒径和zeta电位分别为220.28 nm和-13.3 mV。FA-QDs-FUA的载药含量为36.85%±1.61%（n = 3）。与游离5-氟尿嘧啶药物相比，5-氟尿嘧啶从FA-QDs-FUA中的释放曲线显示出缓慢且持续的释放行为。细胞实验结果表明，与游离5-氟尿嘧啶相比，FA-QDs-FUA降低了细胞毒性，并且比正常细胞更容易靶向肝细胞癌细胞（SMMC-7721和HepG2）。在5-氟尿嘧啶剂量为4.72 mg/kg时，用FA-QDs-FUA治疗的小鼠比用游离5-氟尿嘧啶治疗的小鼠表现出更好的肿瘤抑制效果。因此，FA-QDs-FUA系统可作为一种有前景的候选物，用于提高5-氟尿嘧啶的疗效和肿瘤靶向特异性，同时毒性有限。
