Yili Zhao

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

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.

Folic acid modified electrospun poly(vinyl alcohol)/polyethyleneimine nanofibers for cancer cell capture applications

Capture and detection of metastatic cancer cells are crucial for diagnosis and treatment of malignant neoplasm. Here, we report the use of folic acid (FA) modified electrospun poly(vinyl alcohol) (PVA)/polyethyleneimine (PEI) nanofibers for cancer cell capture applications. Electrospun PVA/PEI nanofibers crosslinked by glutaraldehyde vapor were modified with FA via a poly(ethylene glycol) (PEG) spacer, followed by acetylation of the fiber surface PEI amines. The formed FA-modified nanofibers were well characterized. The morphology of the electrospun PVA/PEI nanofibers is smooth and uniform despite the surface modification. In addition, the FA-modified nanofibers display good hemocompatibility as confirmed by hemolysis assay. Importantly, the developed FA-modified nanofibers are able to specifically capture cancer cells overexpressing FA receptors, which were validated by quantitative cell counting assay and qualitative confocal microscopy analysis. The developed FA-modified PVA/PEI nanofibers may be used for capturing circulating tumor cells for cancer diagnosis applications.

Capturing hepatocellular carcinoma cells using lactobionic acid-functionalized electrospun polyvinyl alcohol/polyethyleneimine nanofibers

We report a facile approach to immobilizing lactobionic acid (LA) onto electrospun polyvinyl alcohol (PVA)/polyethyleneimine (PEI) nanofibers through a polyethylene glycol (PEG) spacer for capturing hepatocellular carcinoma cells. In this work, electrospun PVA/PEI nanofibers were crosslinked using glutaraldehyde vapor, covalently conjugated with PEGylated LA via an N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDC) coupling reaction, followed by acetylation of the remaining PEI amines on the fiber surface. The formed LA-functionalized nanofibers were characterized via scanning electron microscopy and attenuated total reflectance-Fourier transform infrared spectroscopy. We show that the fiber morphology does not significantly change after fiber surface modification. The functionalized nanofibers display good hemocompatibility and superior capability to capture asialoglycoprotein receptor (ASGPR)-overexpressing hepatocellular carcinoma cells in vitro via a ligand–receptor interaction. The developed LA-modified PVA/PEI nanofibers may be applied to capture circulating tumor cells for cancer diagnosis applications.

Attapulgite-doped electrospun poly(lactic-co-glycolic acid) nanofibers enable enhanced osteogenic differentiation of human mesenchymal stem cells

The extracellular matrix mimicking property of electrospun polymer nanofibers affords their uses as an ideal scaffold material for differentiation of human mesenchymal stem cells (hMSCs), which is important for various tissue engineering applications. Here, we report the fabrication of electrospun poly(lactic-co-glycolic acid) (PLGA) nanofibers incorporated with attapulgite (ATT) nanorods, a clay material for osteogenic differentiation of hMSCs. We show that the incorporation of ATT nanorods does not significantly change the uniform morphology and the hemocompatibility of the PLGA nanofibers; instead the surface hydrophilicity and cytocompatibility of the hybrid nanofibers are slightly improved after doping with ATT. Alkaline phosphatase activity, osteocalcin secretion, calcium content, and von Kossa staining assays reveal that hMSCs are able to be differentiated to form osteoblast-like cells onto both PLGA and PLGA–ATT composite nanofibers in osteogenic medium. Most strikingly, the doped ATT within the PLGA nanofibers is able to induce the osteoblastic differentiation of hMSCs in growth medium without the inducing factor of dexamethasone. The fabricated organic/inorganic hybrid ATT-doped PLGA nanofibers may find many applications in the field of tissue engineering and regenerative medicine.

The assembly of polyethyleneimine-entrapped gold nanoparticles onto filter paper for catalytic applications

A facile approach to assembling polyethyleneimine (PEI)-entrapped gold nanoparticles (Au PENPs) onto filter paper is reported. In this work, Au PENPs with an Au core size of 3.2 ± 0.8 nm were formed using PEI as a template, followed by adsorption onto filter paper. The formed Au PENP-containing filter paper was characterized by various techniques. We show that the Au PENPs are able to be adsorbed onto filter paper likely due to the microfibrous structure of the paper and the electrostatic interaction between the positively charged Au PENPs and the negatively charged filter paper. Furthermore, we demonstrate that the Au PENP-assembled filter paper displays an excellent catalytic activity and reusability to converting 4-nitrophenol to 4-aminophenol. Such a development of Au PENP-assembled filter paper may be applicable for the immobilization of other metal NPs onto filter paper for various applications in catalysis, sensing, and biomedical sciences.

Electrospun attapulgite-doped poly(lactic-co-glycolic acid) nanofibers for osteogenic differentiation of human mesenchymal stem cells

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Electrospun PEGylated PLGA nanofibers for drug encapsulation and release

We report the fabrication of electrospun nanofibers of polyethylene glycol (PEG)-modified poly (lactic-co-glycolic acid) (PLGA) with a fast release profile for biomedical applications. In this work, PLGA was first covalently modified with methoxy poly (ethylene glycol) amine (mPEG-NH2). The formed PEGylated PLGA (PLGA-PEG) was then mixed with a model drug amoxicillin (AMX) for subsequent fabrication of drug-loaded electrospun nanofibers. The synthesized PLGA-PEG conjugate and the formed drug-loaded PLGA-PEG nanofibers were characterized using different techniques. We show that the modification of PEG does not lead to an appreciable change in the uniform and smooth morphology of PLGA nanofibers. Importantly, the PEGylation modification affords a faster release profile of the encapsulated drug than pure PLGA nanofibers without PEGylation, which may be ascribed to the improved hydrophilicity of the PLGA-PEG polymer. Furthermore, antibacterial activity assay data reveal that the drug-loaded PLGA-PEG nanofibers are able to inhibit the growth of a model bacterium S. aureus. Finally, the hemocompatibility of the drug-loaded PLGA-PEG nanofibers was evaluated by hemolysis and anticoagulant assays, and the cytocompatibility of the fibers was confirmed by cell viability assay and cell morphology observation. We show that the formed drug-loaded PLGA-PEG nanofibers have an excellent hemocompatibility and cytocompatibility. The developed electrospun PLGA-PEG nanofibers may find various applications in the fields of tissue engineering and pharmaceutical sciences.

CHAPTER 14:Biocompatible Electrospun Polymer–Halloysite Nanofibers for Sustained Release

Fabrication of nanofiber-based drug delivery systems with controlled release properties is of general interest in the biomedical sciences. The micro-nano scale organization and high porosity of electrospun membranes, which is similar to the natural extracellular matrix, is favorable for adhesion and proliferation of cells and decreases the immune response. The incorporation of drug-loaded halloysite within the electrospinning nanofibers is able to improve the tensile strength and maintain the three-dimensional structure of the nanofibrous mats. The “nano in nano” composite is a promising architectural approach for the design of a sustained drug delivery vehicle that combines the drug-loading capability of nanoparticles or nanotubes and electrospinning technology. With improved mechanical durability, sustained drug release profile, good cytocompatibility, and non-compromised therapeutic efficacy, the developed biocompatible electrospun polymer/halloysite nanofibers drug delivery system may be used as therapeutic scaffold materials for tissue engineering and drug delivery applications. In this chapter, we review the recent progress of biocompatible electrospun polymer–halloysite nanofibers for sustained release, and biomedical applications.