Folic Acid Modified Electrospun Nanofibers For Cancer Cell Capture Applications

Circulating tumor cells (CTCs) are a small amount of malignant ones inperipheral blood, originated from the primary tumor or metastases. The detection ofCTCs may contribute to studying the mechanism of cancer metastasis, providingpotential prognostic value, guiding the treatments, judging the therapeutic efficacyand monitoring the recurrence or metastasis. The research of cancer cell capture playsa significant role in early detection of potential fatal cancer metastases.Electrospinning is an effective technology which can produce fibers on nano-ormicro-scale. The formed nanofibers have a great amount of specific surface area andcan be easily modified on the surface. At the same time, the nanofibers are able tosimulate natural extracellular matrix, providing a good micro environment for celladhesion, proliferation and other physiological functions. Because of non-specificityand low sensitivity of cancer cell capture materials, many cancers are not be able to bediagnosed in the early stage, threatening the human’s health. According to the reports,electrospun nanofibers can provide a large number of cell contact sites, thereforeincreasing the number of captured cells per unit volume. Furthermore, through surfacemodification, the capturing sensitivity and specificity to cancer cells can be enhanced.In this study, the PEGylated folic acid (FA) was conjugated to the surface ofPolyvinyl alcohol/Polyethyleneimine (PVA/PEI) electrospun nanofibers for thetargeting capture of cancer cells. FA was first attached to polyethylene glycol (PEG)with a carboxylate group at one end and an amino group at the other end(NH2-PEG-COOH) via N-(3-dimethy-laminopropyl)-N’-ethylcarbodiimidehydrochloride (EDC)/N-Hydroxysuccinimide (NHS) coupling reaction to formFA-PEG-COOH segments. The PVA/PEI nanofibers were then formed by electrospun technique and crosslinked using glutaraldehyde vapor. At last, the nanofibers werecovalently conjugated with FA-PEG-COOH via EDC reaction, followed byacetylation of the remaining PEI amines. The formed FA-modified nanofibers werecharacterized by different techniques. Our results showed that the electrospunPVA/PEI nanofibers with a diameter of425±60.8nm have a smooth and uniformmorphology. Even after glutaraldehyde vapor crosslinking and surface modification,the fiber morphology did not change significantly and mechanical propertiesincluding Young’s modulus and Tensile strength had been improved. The hemolysisassay demonstrated good hemocompatibility of the functionalized nanofibers. Bothcell observation with laser confocal microscope and cell counting indicated thatcompared to nanofibers without FA, the FA-modified nanofibers exhibit superiorcapability to capture U87MG cells overexpressing high-affinity FA receptors.Therefore, the formed FA-modified PVA/PEI nanofibers in this study show a greatpotential to be used to capture circulating tumor cells for cancer diagnosis.