Hee-Man Yang

HER2/neu Antibody Conjugated Poly(amino acid)-Coated Iron Oxide Nanoparticles for Breast Cancer MR Imaging

Superparamagnetic iron oxide nanoparticles are widely used as nanoprobes for magnetic resonance imaging (MRI). Water-soluble iron oxide nanoparticles were synthesized by coating iron oxide nanoparticles with a hydrophilic, biocompatible, biodegradable poly(amino acid) derivative, poly(2-hydroxyethyl aspartamide) graft copolymer for negative contrast enhancement on T2 weighted MRI. HER2/neu antibodies were conjugated on the surface of poly(amino acid) coated iron oxide nanoparticles for the detection of breast cancer. The antibody-grafted iron oxide nanoparticles (PAION-Ab) were about 31.1 nm in diameter. The T2 relaxivity of PAION-Ab was 246 L·mmol(-1)·sec(-1) greater than that of the commercial product such as Feridex. PAION-Ab showed low cytotoxicity even at relatively high concentrations. Furthermore, Prussian blue staining and in vitro MRI study with SKBR-3, breast cancer cells overexpressing HER2/neu receptors indicated that PAION-Ab exhibited excellent cancer cell detection ability and enhanced signal intensities in the T2-weighted image.

Poly(amino acid)-coated iron oxide nanoparticles as ultra-small magnetic resonance probes

A biocompatible and water-soluble poly(amino acid) derivative, with a hydrophilic backbone and side chains facilitating linkage to the surfaces of nanoparticles was used to coat hydrophobic Fe3O4nanoparticles. Such nanoparticles, (4–11 nm), were coated by coordinate bonding and hydrophobic interactions with a hydrophilic poly(amino acid) derivative, poly(2-hydroxyethyl aspartamide). This is a new method for the transfer of hydrophobic nanoparticles from organic solvents into water. The biocompatible poly(amino acid)-coated Fe3O4nanoparticles were smaller than 30 nm in aqueous solutions, extremely stable, and maintained their stability even after several lyophilizations. The poly(amino acid)-coated nanoparticles showed no cytotoxicity, good saturation magnetization, and high T2 relaxivity coefficients (r2 values). The poly(amino acid)-coated Fe3O4nanoparticles demonstrate strong potential in bioapplications such as magnetic resonance imaging (MRI).

Poly(amino acid)s micelle-mediated assembly of magnetite nanoparticles for ultra-sensitive long-term MR imaging of tumors

Micelles composed of a novel weakly cationic poly(amino acid)s shell and clustered magnetite nanoparticles as a core were prepared and evaluated as a potent MR imaging contrast agent based on their superior physicochemical and magnetic properties and the effective MR imaging of cancer in vitro and in vivo.

A direct surface modification of iron oxide nanoparticles with various poly(amino acid)s for use as magnetic resonance probes

Water soluble and biocompatible iron oxide nanoparticles coated with poly(aspartic acid) (PAsp), poly(asparagines) (PAsn), poly(2-hydroxy-ethyl L-aspartamide) (PHEA), and poly-α,β-(N-2-dimethylaminoethyl L-aspartamide) (PDMAEA) were prepared by hydrophobic interaction between hydrophobic iron oxide nanoparticles and each amphiphilic poly(amino acid)s graft polymer. The octadecyl side chain grafted poly(succinimide)(PSI-g-C(18)), used as a precursor polymer, was easily aminolyzed with nucleophilic compounds to form various poly(amino acid)s graft polymer (PAsp-g-C(18), PAsn-g-C(18), PHEA-g-C(18), PDMAEA-g-C(18),) and simultaneously stabilize the dispersion of iron oxide nanoparticles in aqueous solution. The diameters of the poly(amino acid)s coated iron oxide nanoparticles (PAIONs) were smaller than 30 nm in aqueous solution, extremely stable in aqueous solutions with a wide range of pH and salt concentrations. Further, all the PAIONs showed excellent MR signal intensities (high r(2) values) and the cellular uptake property of the PAIONs was also evaluated.

Core–shell nanogel of PEG–poly(aspartic acid) and its pH-responsive release of rh-insulin

A new synthesis approach for the preparation of pH-responsive nanogels via core hydrolysis of cross-linked polymer micelles is proposed. The core–shell nanogels of poly(ethylene glycol)–poly(aspartic acid) exhibited a pH-responsive swelling behavior attributed to the ionization of aspartic acids, and the swelling of the nanogels depended on the cross-linking density. Small-angle neutron scattering (SANS) data were used to investigate the structure and swelling behavior of the nanogels via fitting analysis based on a new model equation that describes two distinguishable scattering intensities that arise from the particle structure and the fluctuation of polymer networks. We estimated that the nanogel core can absorb a volume of water molecules up to 30 times the volume of the polymer itself. The hydrophilic nanogels were able to entrap a proteindrug, rh-insulin, and the drug release was retarded under acidic conditions due to deswelling of the nanogels.

Removal of Radioactive Cesium Using Prussian Blue Magnetic Nanoparticles

Radioactive cesium (137Cs) has inevitably become a human concern due to exposure from nuclear power plants and nuclear accident releases. Many efforts have been focused on removing cesium and the remediation of the contaminated environment. In this study, we elucidated the ability of Prussian blue-coated magnetic nanoparticles to eliminate cesium from radioactive contaminated waste. Thus, the obtained Prussian blue-coated magnetic nanoparticles were then characterized and examined for their physical and radioactive cesium adsorption properties. This Prussian blue-coated magnetic nanoparticle-based cesium magnetic sorbent can offer great potential for use in in situ remediation.

Folate-conjugated cross-linked magnetic nanoparticles as potential magnetic resonance probes for in vivo cancer imaging

Superparamagnetic iron oxide nanoparticles are widely used as nanoprobes for magnetic resonance imaging (MRI). In this study, a novel type of cross-linked magnetic nanoparticle was developed in an effort to improve the structural stability of amphiphilic polymer-coated iron oxide nanoparticles. Iron oxide nanocrystals were coated with a cross-linkable amphiphilic graft copolymer, poly(succinimide) grafted with folate-conjugated polyethylene glycol (PEG) and alkyl chains. The tumor-specific targeting ligand, folate, was included to target and detect cancer cells. The hydrophobic portions of the amphiphilic copolymer on the surfaces of the nanoparticles were cross-linked via an aminolysis reaction between the succinimide units and a bifunctional primary amine. The folate-conjugated cross-linked magnetic nanoparticles (F-CLMNPs) were 40 nm in diameter and displayed a low cytotoxicity, even at relatively high concentrations. The F-CLMNPs exhibited highly efficient intracellular uptake into KB cells, which overexpress the folate receptor, as determined by fluorescence microscopy, flow cytometry, and Prussian blue staining. In vivo MR images of a mouse bearing a KB cell tumor displayed a 75% drop in the T2 signal in the tumor tissues within 3 hours. These results indicated that the F-CLMNPs accumulated at the tumor site and were highly effective for tumor detection using in vivo MRI techniques.

Polymer-hybridized liposomes of poly(amino acid) derivatives as transepidermal carriers.

This work describes the use of a novel transepidermal drug carrier system composed of phospholipids and amphiphilc poly(amino acid)s. We polymerized poly(asparagine) grafted with octadecylamine (PAsn-g-C18), poly(aspartic acid) grafted with octadecylamine (PAsp-g-C18), and poly(aspartic acid) grafted with phytosphingosine (PAsp-g-PHS). We then prepared polymer hybridized liposomes (PHL) anchored with alkyl grafted poly(amino acid)s and encapsulated hydrolyzed ginseng saponins (HGS). We confirmed that the liposomes and PHL reduce the cytotoxicity of HGS, which was not observed with polymeric nano-carriers. A quantitative analysis of the amount of penetrated HGS using the Franz cell method revealed that skin permeation of the lipophilic drugs loaded in liposomes was enhanced by the incorporation of amphiphilic poly(amino acid)s. Fluorescence microscopy observations also demonstrated excellent skin permeation performance of PHL anchored with PAsp-g-PHS. PHL showed better structural stability than liposomes in an O/W emulsion. PHL considerably improved the chemical stability of HGS compared to the liposomes. It is thought that the skin permeability of encapsulated bioactive molecules could be affected by the vesicle structure, membrane fluidity, and the type of anchored polymer.

Aqueous self-assembly of amphiphilic nanocrystallo-polymers and their surface-active properties

The self-assembly of nanocrystals using a bottom-up approach is advantageous because it is possible to control their direct structure at a nanometre length scale and their collective optical and electronic properties. Here, we present the novel fabrication and aqueous self-assembly of amphiphilic nanocrystallo-polymers. Hydrophobic nanocrystals are used as the hydrophobic component of amphiphiles, and they can drive the hydrophobic interaction-mediated direct self-assembly to create various nanostructures, such as spherical aggregates, core-shell unimolecular micelles, and cylinders. The nanocrystals can be uniformly arranged in the core of the nanostructures. We further show that the amphiphilic nanocrystallo-polymers have dynamic self-assembling and surface-active properties.

Removal of cesium ions from clays by cationic surfactant intercalation

We propose a new approach to remediate cesium-contaminated clays based on intercalation of the cationic surfactant dodecyltrimethylammonium bromide (DTAB) into clay interlayers. Intercalation of DTAB was found to occur very rapidly and involved exchanging interlayer cations. The reaction yielded efficient cesium desorption (∼97%), including of a large amount of otherwise non-desorbable cesium ions by cation exchange with ammonium ions. In addition, the intercalation of DTAB afforded an expansion of the interlayers, and an enhanced desorption of Cs by cation exchange with ammonium ions even at low concentrations of DTAB. Finally, the residual intercalated surfactants were easily removed by a decomposition reaction with hydrogen peroxide in the presence of Cu2+/Fe2+ catalysts.