Zhao Yili, Zhu Xiaoyue, Liu Hui, Luo Yu, Wang Shige, Shen Mingwu, Zhu Meifang, Shi Xiangyang
State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Materials Science and Engineering, Donghua University, Shanghai 201620, People's Republic of China.
J Mater Chem B. 2014 Nov 14;2(42):7384-7393. doi: 10.1039/c4tb01278j. Epub 2014 Sep 29.
Cancer cell metastasis causes 90% of cancer patient death. Detection and targeted capture of cancer cells in vitro are of paramount importance. The development of novel nanodevices for cancer cell capture applications, however, still remains a great challenge. Here we report a facile approach to fabricating multifunctional dendrimer-modified electrospun cellulose acetate (CA) nanofibers for targeted cancer cell capture applications. In this study, hydrolyzed electrospun CA nanofibers with negative surface charge were assembled layer-by-layer with a bilayer of poly(diallyldimethylammonium chloride) (PDADMAC) and polyacrylic acid (PAA) via electrostatic interactions. Thereafter, amine-terminated generation 5 poly(amidoamine) dendrimers pre-modified with folic acid (FA) and fluorescein isothiocyanate were covalently conjugated onto the bilayer-assembled nanofibers via the 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride coupling reaction, followed by acetylation to neutralize the remaining dendrimer surface amines. The formation of electrospun CA nanofibers, assembly of the PDADMAC/PAA bilayer onto the CA nanofibers, and the dendrimer modification on the nanofibers were characterized via different techniques. The formed dendrimer-modified CA nanofibers were then used to capture cancer cells overexpressing FA receptors. We show that the bilayer self-assembly and the subsequent dendrimer modification do not appreciably change the fiber morphology. Importantly, the modification of FA-targeted multifunctional dendrimers renders the CA nanofibers with superior capability to specifically capture cancer cells (KB cells, a model cancer cell line) overexpressing high-affinity FA receptors. The approach to modifying electrospun nanofibers with multifunctional dendrimers may be extended to fabricate other functional nanodevices for capturing different types of cancer cells.
癌细胞转移导致90%的癌症患者死亡。体外检测和靶向捕获癌细胞至关重要。然而，开发用于癌细胞捕获应用的新型纳米器件仍然是一个巨大的挑战。在此，我们报告了一种简便的方法，用于制造多功能树枝状聚合物修饰的电纺醋酸纤维素（CA）纳米纤维，用于靶向癌细胞捕获应用。在本研究中，具有负表面电荷的水解电纺CA纳米纤维通过静电相互作用与聚二烯丙基二甲基氯化铵（PDADMAC）和聚丙烯酸（PAA）的双层逐层组装。此后，用叶酸（FA）和异硫氰酸荧光素预修饰的胺端基第5代聚酰胺-胺树枝状聚合物通过1-乙基-3-（3-二甲基氨基丙基）碳二亚胺盐酸盐偶联反应共价连接到双层组装的纳米纤维上，随后进行乙酰化以中和剩余的树枝状聚合物表面胺。通过不同技术对电纺CA纳米纤维的形成、PDADMAC/PAA双层在CA纳米纤维上的组装以及纳米纤维上的树枝状聚合物修饰进行了表征。然后将形成的树枝状聚合物修饰的CA纳米纤维用于捕获过表达FA受体的癌细胞。我们表明，双层自组装和随后的树枝状聚合物修饰不会明显改变纤维形态。重要的是，FA靶向多功能树枝状聚合物的修饰使CA纳米纤维具有卓越的能力，能够特异性捕获过表达高亲和力FA受体的癌细胞（KB细胞，一种模型癌细胞系）。用多功能树枝状聚合物修饰电纺纳米纤维的方法可能会扩展到制造用于捕获不同类型癌细胞的其他功能性纳米器件。
