Folic acid-tagged titanium dioxide nanoparticles for enhanced anticancer effect in osteosarcoma cells
Folic acid-tagged titanium dioxide nanoparticles for enhanced anticancer effect in osteosarcoma cells
复制标题
DOI：
10.1016/j.msec.2017.03.027
复制
发表时间：
2017-07-01
影响因子：
7.9
通讯作者：
Liu, Wei-dong
中科院分区：
文献类型：
--
作者：
Ai, Jin-wei;Liu, Bin;Liu, Wei-dong
在这项研究中，叶酸表面修饰的二氧化钛纳米粒子（FA-TiNP）的制备作为一个合适的替代传统的化疗药物治疗人骨肉瘤。聚合物在纳米粒子表面组装后，TiNP的粒径明显增大，呈球形。FA-TiNP在骨肉瘤癌细胞中表现出比裸TiNP更上级的抗癌效果。其原因可能是由于FA与癌细胞中过表达的叶酸受体的特异性相互作用。特别是FA-TiNP处理的细胞表现出染色质浓缩、细胞皱缩和膜起泡。FA-TiNP显示出显著更高的癌细胞凋亡，其中近38%的细胞处于凋亡室中（早期和晚期），而TiNP仅为16%。FA-TiNP处理组的较高比例的膜联蛋白V阳性细胞主要归因于TiO 2的较高细胞内摄取。重要的是，FA-TiNP将亚GO群体增加至接近25%，表明其上级抗癌作用。结果清楚地表明，FA-TiNP诱导更大的活性氧（ROS）产生，导致更高的亚GO细胞群和更高的细胞凋亡。FA-TiNP显示出细胞色素C（Cyt C）的显著更高表达，同时裂解的caspase-3和PARP的表达显著增加。总体而言，结果表明，用特异性靶向部分对TiNP进行表面修饰可以提高成功治疗癌症疾病的机会。(C)2017爱思唯尔B. V.保留所有权利。
In this study, folic acid surface modified-Titanium dioxide nanoparticles (FA-TiNP) were prepared as a suitable alternative to conventional chemotherapeutic agents to treat human osteosarcoma. The particle size of TiNP increased marked after polymer assembly on the nanoparticles (NP) surface with a spherical morphology. FA-TiNP exhibited a superior anticancer effect in osteosarcoma cancer cells compared to that of bare TiNP. The reason might due to the specific interaction of FA with the folate receptor which is overexpressed in the cancer cells. Especially, FA-TiNP treated cells exhibited chromatin condensation, cell shrinkage and membrane blebbing. FA-TiNP showed significantly higher cancer cell apoptosis with nearly 38% of cells in apoptosis chamber (early and late) compared to only similar to 16% for TiNP. The higher proportion of Annexin V positive cells for FA-TiNP treated group was mainly attributed to the higher intracellular uptake of the TiO2. Importantly, FA-TiNP increased the sub-GO population to similar to 25% indicating its superior anticancer effect. The results clearly indicated that FA-TiNP induced greater reactive oxygen species (ROS) generation that resulted in higher sub-GO cell population with higher cell apoptosis. FA-TiNP showed a remarkably higher expression of cytochrome C (Cyt C) with a marked increase in the expression of cleaved caspase-3 and PARP. Overall, results suggest that surface modification of TiNP with a specific targeting moiety could enhance the chances of having successful therapies for cancer diseases. (C) 2017 Elsevier B.V. All rights reserved.