San Kyeong

Comparison of endothelialization and neointimal formation with stents coated with antibodies against CD34 and vascular endothelial-cadherin.

Vascular endothelial-cadherin (VE-cadherin) is exclusively expressed on the late endothelial progenitor cells (EPC). Therefore, VE-cadherin could be an ideal target surface molecule to capture circulating late EPC. In the present study, we evaluated whether anti-VE-cadherin antibody-coated stents (VE-cad stents) might accelerate endothelial recovery and reduce neointimal formation more than anti-CD34 antibody-coated stents (CD34 stents) through the superior ability to capture the late EPC. The stainless steel stents were coated with anti-human VE-cadherin antibodies or anti-human CD34 antibodies under the same condition. In vitro, VE-cad stents showed higher number of adhering EPC (823.6 ± 182.2 versus 379.2 ± 137.2 cells per HPF, p < 0.001). VE-cad stents also demonstrated better specific capturing of cells with endothelial lineage markers than CD34 stents did in flow cytometric analysis. VE-cad stents showed more effective re-endothelialization after 1 h, 24 h, and 3 days in vivo. At 42 days, VE-cad stents demonstrated significantly smaller neointima area (0.92 ± 0.38 versus 1.24 ± 0.41 mm(2), p = 0.002) and significantly lower PCNA positive cells in neointima (1684.8 ± 658.8/mm(2) versus 2681.7 ± 375.1/mm(2), p = 0.008), compared with CD34 stents. In conclusion, VE-cad stents captured EPC and endothelial cells more selectively in vitro, accelerated re-endothelialization over stents, and reduced neointimal formation in vivo, compared with CD34 stents.

Stent Coated With Antibody Against Vascular Endothelial-Cadherin Captures Endothelial Progenitor Cells, Accelerates Re-Endothelialization, and Reduces Neointimal Formation

Objective—In contrast to CD34, vascular endothelial-cadherin (VE-cadherin) is exclusively expressed on the late endothelial progenitor cells (EPC) whereas not on the early or myeloid EPC. Thus, VE-cadherin could be an ideal target surface molecule to capture circulating late EPC. In the present study, we evaluated whether anti-VE–cadherin antibody-coated stents (VE-cad stents) might accelerate endothelial recovery and reduce neointimal formation through the ability of capturing EPC. Methods and Results—The stainless steel stents were coated with rabbit polyclonal anti-human VE-cadherin antibodies and exposed to EPC for 30 minutes in vitro. The number of EPC that adhered to the surface of VE-cad stents was significantly higher than bare metal stents (BMS) in vitro, which was obliterated by pretreatment of VE-cad stent with soluble VE-cadherin proteins. We deployed VE-cad stents and BMS in the rabbit right and left iliac arteries, respectively. At 48 hours after stent deployment in vivo, CD-31–positive endothelial cells adhered to VE-cad stent significantly more than to BMS. At 3 days, scanning electron microscopy showed that over 90% surface of VE-cad stents was covered with endothelial cells, which was significantly different from BMS. At 42 days, neointimal area that was filled with smooth muscle cells positive for actin or calponin was significantly smaller in VE-cad stents than in BMS by histological analysis (0.95±0.22 versus 1.34±0.43 mm2, respectively, P=0.02). Immuno-histochemical analysis revealed that infiltration of inflammatory cells was not significantly different between 2 stents. Conclusion—VE-cad stents captured EPC successfully in vitro, accelerated endothelial recovery on stent, and eventually reduced neointimal formation in vivo.

Fabrication of biofunctional stents with endothelial progenitor cell specificity for vascular re-endothelialization.

Endothelial progenitor cells (EPCs) have been identified as a crucial factor for re-endothelialization after stenting, resulting in the prevention of stent thrombosis and neointimal hyperplasia. Because EPCs can be introduced by antibody-antigen interactions, the suitable choice of antibody and the biocompatible surface modification technology including antibody immobilization are essential for developing an EPC-capturing stent. In this study, we fabricated a biofunctional stent with EPC specificity by grafting a hydrophilic polymer and consecutively immobilizing the antibody against vascular endothelial cadherin (VE-cadherin) which is one of the specific EPC surface markers. The surface of a stainless steel stent was sequentially modified by acid-treatment, silanization and covalent attachment of polymers not only to improve biocompatibility but also to introduce functional groups on the stent surface. The surface-modified stent immobilized anti-VE-cadherin antibodies, and the EPCs were remarkably captured whereas THP-1s, human acute monocytic leukemia cells, were not adsorbed on the stent. Furthermore, we confirmed that the recruited EPCs developed the endothelial cell layers on the antibody-conjugated stent. These positive in vitro results will encourage the extensive application of biofunctional surface modification technology for a variety of medical devices.

Facile method for preparation of silica coated monodisperse superparamagnetic microspheres

This paper presents a facile method for preparation of silica coated monodisperse superparamagnetic microsphere. Herein, monodisperse porous polystyrene-divinylbenzene microbeads were prepared by seeded emulsion polymerization and subsequently sulfonated with acetic acid/H2SO4. The as-prepared sulfonated macroporous beads were magnetized in presence of Fe2+/Fe3+ under alkaline condition and were subjected to silica coating by sol-gel process, providing water compatibility, easily modifiable surface form, and chemical stability. FE-SEM, TEM, FT-IR, and TGA were employed to characterize the silica coated monodisperse magnetic beads (∼7.5 µm). The proposed monodisperse magnetic beads can be used as mobile solid phase particles candidate for protein and DNA separation.

Direct Identification of On-Bead Peptides Using Surface-Enhanced Raman Spectroscopic Barcoding System for High-Throughput Bioanalysis

Recently, preparation and screening of compound libraries remain one of the most challenging tasks in drug discovery, biomarker detection, and biomolecular profiling processes. So far, several distinct encoding/decoding methods such as chemical encoding, graphical encoding, and optical encoding have been reported to identify those libraries. In this paper, a simple and efficient surface-enhanced Raman spectroscopic (SERS) barcoding method using highly sensitive SERS nanoparticles (SERS ID) is presented. The 44 kinds of SERS IDs were able to generate simple codes and could possibly generate more than one million kinds of codes by incorporating combinations of different SERS IDs. The barcoding method exhibited high stability and reliability under bioassay conditions. The SERS ID encoding based screening platform can identify the peptide ligand on the bead and also quantify its binding affinity for specific protein. We believe that our SERS barcoding technology is a promising method in the screening of one-bead-one-compound (OBOC) libraries for drug discovery.

Double-Layer Magnetic Nanoparticle-Embedded Silica Particles for Efficient Bio-Separation

Superparamagnetic Fe3O4 nanoparticles (NPs) based nanomaterials have been exploited in various biotechnology fields including biomolecule separation. However, slow accumulation of Fe3O4 NPs by magnets may limit broad applications of Fe3O4 NP-based nanomaterials. In this study, we report fabrication of Fe3O4 NPs double-layered silica nanoparticles (DL MNPs) with a silica core and highly packed Fe3O4 NPs layers. The DL MNPs had a superparamagnetic property and efficient accumulation kinetics under an external magnetic field. Moreover, the magnetic field-exposed DL MNPs show quantitative accumulation, whereas Fe3O4 NPs single-layered silica nanoparticles (SL MNPs) and silica-coated Fe3O4 NPs produced a saturated plateau under full recovery of the NPs. DL MNPs are promising nanomaterials with great potential to separate and analyze biomolecules.

Plasmon-enhanced dye-sensitized solar cells using SiO2 spheres decorated with tightly assembled silver nanoparticles

SiO2 spheres decorated with tightly assembled silver nanoparticles were incorporated into the photoanode of a dye-sensitized solar cell. Localized surface plasmon resonance from the assembled Ag nanoparticles increased the light absorption throughout the wide visible light range. This plasmon-enhanced light absorption resulted in a significant improvement in the device performance.

Preparation of plasmonic magnetic nanoparticles and their light scattering properties

Fe3O4@SiO2@Au nanoparticles (NPs) that have plasmonic and magnetic properties were prepared by simple immobilization method of Au NPs to silica coated magnetic NPs. The Fe3O4@SiO2@Au exhibit 5 times higher light scattering compared to the same sized gold NPs. The experimental results were supported by the simulations.

Fabrication of mono-dispersed silica-coated quantum dot-assembled magnetic nanoparticles†

Multifunctional nanoparticles (NPs) with magnetic and luminescent properties have garnered considerable attention in various fields of biomedical and physiological applications. In this study, we report the fabrication of QD-embedded silica NPs with an iron oxide NP core (Fe3O4@SiO2@QDs NPs) that has dual functional properties. The Fe3O4@SiO2@QDs NPs were mono-dispersed in size and exhibited super-paramagnetic and highly fluorescent properties. Most of the Fe3O4@SiO2@QDs NPs were naturally internalized into MDA-MB-231 human breast cancer cells, and the NP containing cells were successfully sorted by utilizing both fluorescence flow cytometry and a magnetic field. Results indicate that the Fe3O4@SiO2@QDs NPs have great potential for multimodal cell separation.

Quantum dot-assembled nanoparticles with polydiacetylene supramolecule toward label-free, multiplexed optical detection.

Quantum dot (QD)-assembled silica nanoparticles bearing a polydiacetylene (PDA) supramolecule on their surface (SiO(2)@QDs@PDA NPs) were developed for label-free and multiplexed detection of biological molecules. Two types of QD-assembled silica NPs (SiO(2)@QDs NPs) were prepared and coated with the PDA supramolecule via photo-induced polymerization of 10,12-pentacosadiynoic acid. One of the SiO(2)@QDs NPs was embedded with blue-QDs, and the other was embedded with green-QDs for encoding. The resulting SiO(2)@QDs@PDA NPs showed discrete QD photoluminescence for encoding as well as PDA fluorescence for sensing a target without interference or overlap. Under heating stress of the SiO(2)@QDs@PDA NPs, the color of the PDA changed from blue to red, which allowed us to observe the fluorescence emitted from red PDA. The mixture of two different SiO(2)@QDs@PDA NPs, SiO(2)@QDs@blue-PDA NPs not emitting the fluorescence of PDA and SiO(2)@QDs@red-PDA NPs where stress was brought onto turn on the PDA fluorescence, was effectively imaged and readily distinguished via fluorescence microscopy, indicating their potential for label-free and multiplexed detection of target molecules.