Dendrimer-functionalized electrospun cellulose acetate nanofibers for targeted cancer cell capture applications

Abstract

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.