Wang Jianting, Wang Ming, Zheng Mingming, Guo Qiong, Wang Yafan, Wang Heqing, Xie Xiangrong, Huang Fenghong, Gong Renmin
College of Life Science, Anhui Normal University, Wuhu, 241000, PR China.
Anhui Province Key Laboratory of Biological Macro-molecules Research, Wannan Medical College, Wuhu, 241002, PR China; Department of Biochemistry and Molecular Biology, Wannan Medical College, Wuhu, 241002, PR China.
Colloids Surf B Biointerfaces. 2015 May 1;129:63-70. doi: 10.1016/j.colsurfb.2015.03.028. Epub 2015 Mar 18.
Self-assembled core/shell nanoparticles (NPs) were synthesized from water-soluble alginate substituted by hydrophobic phytosterols. Folate, a cancer-cell-specific ligand, was conjugated to the phytosterol-alginate (PA) NPs for targeting folate-receptor-overexpressing cancer cells. The physicochemical properties of folate-phytosterol-alginate (FPA) NPs were characterized by nuclear magnetic resonance, transmission electron microscopy, dynamic light scattering, electrophoretic light scattering, and fluorescence spectroscopy. Doxorubicin (DOX), an anticancer drug, was entrapped inside prepared NPs by dialysis method. The identification of prepared FPA NPs to folate-receptor-overexpressing cancer cells (KB cells) was confirmed by cytotoxicity and folate competition assays. Compared to the pure DOX and DOX/PA NPs, the DOX/FPA NPs had lower IC50 value to KB cells because of folate-receptor-mediated endocytosis process and the cytotoxicity of DOX/FPA NPs to KB cells could be competitively inhibited by free folate. The cellular uptake and internalization of pure DOX and DOX/FPA NPs was confirmed by confocal laser scanning microscopy image and the higher intracellular uptake of drug for DOX/FPA NPs over pure DOX was observed. The FPA NPs had the potential as a promising carrier to target drugs to cancer cells overexpressing folate receptors and avoid cytotoxicity to normal tissues.
自组装核/壳纳米颗粒（NPs）由经疏水植物甾醇取代的水溶性藻酸盐合成。叶酸是一种癌细胞特异性配体，与植物甾醇-藻酸盐（PA）纳米颗粒偶联，用于靶向叶酸受体过表达的癌细胞。通过核磁共振、透射电子显微镜、动态光散射、电泳光散射和荧光光谱对叶酸-植物甾醇-藻酸盐（FPA）纳米颗粒的物理化学性质进行了表征。采用透析法将抗癌药物阿霉素（DOX）包裹在制备的纳米颗粒内。通过细胞毒性和叶酸竞争试验证实了制备的FPA纳米颗粒对叶酸受体过表达癌细胞（KB细胞）的识别能力。与纯DOX和DOX/PA纳米颗粒相比，DOX/FPA纳米颗粒对KB细胞的IC50值较低，这是由于叶酸受体介导的内吞作用过程，并且游离叶酸可以竞争性抑制DOX/FPA纳米颗粒对KB细胞的细胞毒性。通过共聚焦激光扫描显微镜图像证实了纯DOX和DOX/FPA纳米颗粒的细胞摄取和内化，并且观察到DOX/FPA纳米颗粒比纯DOX具有更高的细胞内药物摄取。FPA纳米颗粒有潜力作为一种有前景的载体，将药物靶向到叶酸受体过表达的癌细胞，并避免对正常组织产生细胞毒性。
