Yang Rui, An YanLi, Miao FengQin, Li MengFei, Liu PeiDang, Tang QiuSha
School of Medicine, Southeast University, Nanjing, Jiangsu Province, People's Republic of China.
Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Nanjing, Jiangsu Province, People's Republic of China.
Int J Nanomedicine. 2014 Sep 4;9:4231-43. doi: 10.2147/IJN.S67210. eCollection 2014.
This study aimed to generate targeted folic acid-conjugated, doxorubicin-loaded, magnetic iron oxide bovine serum albumin nanospheres (FA-DOX-BSA MNPs) that lower the side effects and improve the therapeutic effect of antitumor drugs when combined with hyperthermia and targeting therapy. A new nanodrug using magnetic nanospheres for heating and addition of the folate receptor with cancer cell specificity was prepared. The characteristics of these nanospheres and their antitumor effects in nasopharyngeal carcinoma were explored.
FA-DOX-BSA MNPs comprising encapsulated magnetic iron oxide nanoparticles were prepared using a desolvation cross-linking method. Activated folic acid (N-hydroxysuccinimide ester of folic acid) was conjugated to the surface of albumin nanospheres via amino groups.
Folic acid was successfully expressed on the surface of the nanospheres. Electron microscopy revealed that the FA-DOX-BSA MNPs were nearly spherical and uniform in size, with an average diameter of 180 nm. The nanomaterial could deliver doxorubicin at clinically relevant doses with an entrapment efficiency of 80%. An increasing temperature test revealed that incorporation of magnetic iron oxide into nanospheres could achieve a satisfactory heat treatment temperature at a significantly lower dose when placed in a high-frequency alternating magnetic field. FA-DOX-BSA MNPs showed greater inhibition of tumors than in the absence of folic acid in vitro and in vivo. Compared with chemotherapy alone, hyperthermia combined with chemotherapy was more effective against tumor cells.
Folic acid-conjugated bovine serum albumin nanospheres composed of mixed doxorubicin and magnetic iron oxide cores can enable controlled and targeted delivery of anticancer drugs and may offer a promising alternative to targeted doxorubicin therapy for nasopharyngeal carcinoma.
本研究旨在制备靶向叶酸偶联、负载阿霉素的磁性氧化铁牛血清白蛋白纳米球（FA-DOX-BSA MNPs），以降低副作用，并在与热疗和靶向治疗联合使用时提高抗肿瘤药物的治疗效果。制备了一种利用磁性纳米球进行加热并添加具有癌细胞特异性的叶酸受体的新型纳米药物。探讨了这些纳米球的特性及其在鼻咽癌中的抗肿瘤作用。
采用去溶剂交联法制备了包封磁性氧化铁纳米颗粒的FA-DOX-BSA MNPs。活性叶酸（叶酸的N-羟基琥珀酰亚胺酯）通过氨基偶联到白蛋白纳米球表面。
叶酸成功表达于纳米球表面。电子显微镜显示，FA-DOX-BSA MNPs近乎球形且尺寸均匀，平均直径为180 nm。该纳米材料能够以临床相关剂量递送阿霉素，包封率为80%。升温试验表明，将磁性氧化铁掺入纳米球中，置于高频交变磁场中时，能以显著更低的剂量达到满意的热处理温度。FA-DOX-BSA MNPs在体外和体内均显示出比无叶酸时更强的肿瘤抑制作用。与单纯化疗相比，热疗联合化疗对肿瘤细胞更有效。
由阿霉素和磁性氧化铁核混合组成的叶酸偶联牛血清白蛋白纳米球能够实现抗癌药物的可控靶向递送，可能为鼻咽癌的靶向阿霉素治疗提供一种有前景的替代方案。
