Jian-Ping Xu

Surface engineering of cardiovascular stent with endothelial cell selectivity for in vivo re-endothelialisation.

The in vivo endothelialisation of materials provides a promising strategy for the rapid re-endothelialisation of a cardiovascular implantation. Although many studies have focused on improving the rapid endothelialisation through the immobilisation of bioactive molecules, it should be noted that the endothelial cells (ECs) will compete with other cell types in vivo. Thus, the efforts to partially enhance the EC growth without considering the cell competition might be misleading and meaningless in vivo. In this study, we demonstrated that the competitive growth of human umbilical vein endothelial cells (HUVECs) over human aortic smooth muscle cells (HASMCs) could be increased through the synergic action of the nonspecific resistance to phosphorylcholine and the specific recognition of the REDV peptide. Further in vivo data indicate that the competitive ability of ECs over SMCs, instead of the number of ECs, is a significantly more important criterion for the development of a pure endothelial layer in vivo and thus the attainment of a better anti-restenosis effect. Consequently, the surface tailoring of a stent to obtain high endothelial cell selectivity is likely an effective design criterion for in situ endothelialisation and a possible future solution for the problem of in-stent restenosis.

Polyamidoamine dendrimers surface-engineered with biomimetic phosphorylcholine as potential drug delivery carriers.

Biomimetic acryloyloxyethyl phosphorylcholine (APC) was used to react with generation 5 poly(amido amine) (PAMAM) dendrimers (G5) via the Michael addition reaction between primary amino group of PAMAM dendrimers and acrylic functional group of APC. FTIR and (1)H NMR confirmed the success of surface modification of G5. The primary amino and phosphorylcholine (PC) group numbers of the surface engineered PAMAM dendrimers (G5-PC) were calculated to be 56 and 50 via (1)H NMR and potentiometric titration. Cell viability and cell morphology studies indicated that biomimetic phosphorylcholine surface engineering successfully lowered the cytotoxicity of G5 PAMAM dendrimers. The hydrophobic interior of G5-PC was used to incorporate anti-cancer drug Adriamycin (ADR) and the G5-PC showed sustained releasing behavior for ADR. Cell morphology and viability tests indicated that the drug-loaded G5-PC conjugate could effectively enter the cancer cells and inhibit the growth of cancer cells. Biomimetic phosphorylcholine surface engineered PAMAM dendrimers with lowered cytotoxicity and high cellular penetrating ability showed great potential for the biomedical applications as nanocarrier system.

A novel biomimetic polymer as amphiphilic surfactant for soluble and biocompatible carbon nanotubes (CNTs).

Novel amphiphilic diblock copolymer, cholesterol-end-capped poly(2-methacryloyloxyethyl phosphorylcholine) (CPMPC), which has poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) as hydrophilic segment and cholesterol as hydrophobic segment, was specially designed as amphiphilic surfactant to achieve water-soluble and biocompatible carbon nanotubes (CNTs). The pristine CNTs were facilely dispersed via non-covalently binding the zwitterionic phosphorylcholine-based amphiphile onto the surfaces of the CNTs. It is interesting to find that CPMPC shows better CNTs solubilizing ability compared with the surfactant of pyrene-end-capped poly(2-methacryloyloxyethyl phosphorylcholine) (PPMPC). The biocompatibility of the CPMPC stabilized CNTs was evaluated using cholesterol-end-capped poly(2-(dimethylamino) ethyl methacrylate) (CPDMAEMA), cholesterol-end-capped poly(acrylic acid) (CPAA) and cholesterol-end-capped poly(ethylene oxide) (CPEG) as surfactants for CNTs as controls. While CPDMAEMA stabilized CNTs and CPAA stabilized CNTs showed obvious cytotoxicity, cytotoxicity of this novel zwitterionic phosphorylcholine-based amphiphile stabilized CNTs was not observed as indicated by cell culture. The biocompatible CNTs represent an excellent nano-object for potential biomedical applications.

Highly soluble PEGylated pyrene–gold nanoparticles dyads for sensitive turn-on fluorescent detection of biothiols

Highly soluble fluorescent pyrene derivative with substantially improved fluorescence intensity in aqueous buffer was obtained via PEGylation strategy. The highly soluble PEGylated pyrene (PEO-Py) non-covalently adsorbed onto the surface of gold nanoparticles (Au NPs) to form dyads with quenched fluorescence due to highly efficient energy transfer between PEO-Py and Au NPs. The PEO-Py/Au NPs dyads were used for the sensitive turn-on fluorescent detection of biothiols. The fluorescence of PEO-Py was restored by the addition of cysteine (Cys), indicating that Cys can modulate the energy transfer between PEO-Py and Au NPs. This phenomenon then allowed for the sensitive detection of Cys with a limit of detection (LOD) of 11.4 nM. The linear range of determination of Cys was from 1.25 x 10(-8) to 2.25 x 10(-7) M. None of the other amino acids found in proteins showed obvious interference with the determination. It was important to note that the detection sensitivity of the PEO-Py/Au NPs system was more than 5-fold improved compared with the Py/Au NPs system. In addition, other biothiol molecules, such as glutathione, could also be detected by this sensor system. The method was also successfully applied to the determination of the total content of aminothiols in human plasma. Therefore an easily prepared, inexpensive, high solubility fluorescent probe has been realized and is also expected to detect other biological analytes of interest.

Bowl- and porous sphere-shaped supramolecular assemblies and their application as templates for confined assembly of gold nanoparticles

Polymeric supramolecular assemblies provide a simple and versatile approach to fabricate specific nanostructures and functional nanocomposites in recent years. However, only few supramolecular assembly morphologies, in most cases, micelles and vesicles, have been reported. Herein, novel bowl- and porous sphere-shaped supramolecular assemblies were prepared by self-assembly of a supramolecular copolymer which was formed through end group ionic interaction between hydrophilic poly(2-methacryloyloxyethyl phosphorylcholine) with amino end groups (PMPC-NH2) and hydrophobic polystyrene with carboxyl end groups (PSt-COOH). Furthermore, it is interesting to find that the electrostatic induced supramolecular assemblies possess great potential for further functionalization at the ionic combining interfaces. Gold nanoparticles with a weak positive charge on their surface were assembled in a series of supramolecular assemblies. It was important to note that the gold nanoparticles were preferentially located at the inner interface of the supramolecular assemblies, bowls, porous spheres and others. The present method might be promising to extend to other supramolecular and nanoparticle systems to build spatial distribution precisely controlled nanoparticle–polymer composites.

A novel crosslinkable polymer as drug-loaded coating for biomedical device.

A novel copolymer has been synthesized by the radical polymerization of poly (ethylene oxide) methacrylate, stearyl methacrylate, hydroxypropyl methacrylate and trimethoxysilylpropyl methacrylate. The polymer was characterized by Fourier transform infrared spectroscopy, proton nuclear magnetic resonance (1H-NMR) spectroscopy and gel permeation chromatography. The crosslinkable coating was prepared by dip-coating 5 mg/ml solution in tetrahydrofuran onto glass substrate. A stable crosslinked coating was obtained after curing the coating at 70 °C for 9 h. Contact angle results indicated the possible reorganization of the surface amphiphilic molecule which interpreted the excellent biocompatibility revealed by the results of the platelet adhesion and plasma recalcification time. Rhodamine S and Cibacron Blue were used as model drugs to prepare drug-containing coating at the same conditions. Drug-releasing curves indicated that the mechanism of the release is approximately Fickian release.