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Urine voiding and the presence of a mucus layer on the apical surface of the urothelium are two major challenges towards an effective intravesical drug delivery for bladder malignancies. Improved bioavailability to the underlying bladder tissue could be achieved with delivery vectors that diffuse efficiently through the bladder mucus. Pegylation of delivery vectors remains the existing "gold standard" to enhance mucosal delivery despite known poor cell uptake and reported PEG sensitivity. Here, we showed improved mucopenetration of carboxylated polystyrene (PS) nanoparticles (NPs) passivated with a polydopamine (PDA) surface, at similar level as PEG. While the diffusion of PS NPs in mucus was retarded by ~1000-fold, PS-PDA diffused only 6-fold slower in mucus than water. This enabled faster and deeper penetration of PS-PDA into porcine bladder tissue beneath the mucus layer. The same PDA surface also conferred biocompatibility and enabled photothermal therapy (PTT) with significant surface disruption on an ex vivo porcine bladder model upon localized laser irradiation, which was not possible with PEG. Our outcomes suggested the facile and versatile PDA surface passivation of nanoparticles as an enabler for dual purposes of enhancing mucopenetration and allowing photothermal therapy on bladder tissue, which has not been demonstrated to date., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Mucus is an endogenous viscoelastic biopolymer barrier that limits the entry of foreign pathogens and therapeutic carriers to the underlying mucosal cells. This could be overcome with a hydrophilic and nonpositively charged carrier surface that minimizes interactions with the mucin glycoprotein fibers. Although PEGylation remains an attractive surface strategy to enhance mucopenetration, cell uptake of PEGylated nanoparticles (NPs) often remains poor. Here, we demonstrated polydopamine (PDA) coating to enhance both mucopenetration and cell uptake of NPs. PDA was polymerized on carboxylated polystyrene (PS) NPs to form a PDA coating, and the resulting PS-PDA achieved a similar level of mucopenetration as our PEGylated PS (PS-PEG) positive control in three separate studies: NP-mucin interaction test, transwell assay, and multiple particle tracking. Compared to water, the diffusions of PS-PDA and PS-PEG in reconstituted mucus solution were only 3.5 and 2.4 times slower, respectively, whereas the diffusion of bare PS was slowed by up to 250 times. However, the uptake of PS-PDA (61.2 ± 6.1%) was almost three times higher than PS-PEG (24.6 ± 5.4%) in T24 cells, which were used as a model for underlying mucosal cells. Our results showed a novel unreported functionality of PDA coating in enhancing both mucopenetration and cell uptake of NPs for mucosal drug delivery applications, not possible with conventional PEGylation strategies.

Dopamine (DA) protected by an o-nitrobenzyl functionality on its phenolic group was synthesized as a photolabile catecholamine derivative. This compound, o-nitrobenzyl dopamine (NBDA), was more stable than DA in basic solution at pH 8.5 and will not self-polymerize when protected from light. UV irradiation of a methanolic solution of NBDA at 365 nm for 40 min induced ca. 85% deprotection. Taking advantage of the stability of NBDA, a one-pot spray coating technique for modifying surfaces with polydopamine (PDA) was developed. Using ethylene glycol with Tris buffer (pH 8.5) as the solvent for this technique, stainless steel substrates can be coated with a robust PDA layer. Silver was deposited on the PDA-coated surface after treatment with silver nitrate solution, and >80% of the deposited silver remained on the surface after 1 week immersion in water. The NBDA-Ag surface was highly effective in inhibiting Staphylococcus aureus (S. aureus) biofilm formation.

Treatment of biofilm-related infections in orthopedics remains a serious clinical challenge. It is known that an electric current can significantly enhance the potency of some antibiotics against biofilms (bioelectric effect) but the uncertainty of the mechanisms and the electrolytic cell-like system used in previous studies limit its applications. Herein, the behavior of Staphylococcus aureus (S. aureus) on an electrically conductive polypyrrole/chitosan film upon passage of a direct current (DC) through the film was investigated in the absence and presence of gentamicin. The killing efficacy of the bacteria within the biofilm by gentamicin was greatly enhanced by the DC treatment. From an analysis of the gene expression by the biofilm bacteria after treatment with gentamicin, DC and their combination, it is postulated that the promotion of bacterial autolysis by DC treatment is responsible for the enhanced susceptibility of biofilm S. aureus to gentamicin. This postulate is supported by an increase in the amount of extracellular deoxyribonucleic acid and adenosine triphosphate, and the appearance of disrupted bacterial cells in the biofilm after DC treatment. These findings provide a new insight into the interaction between DC and bacteria, and offer potential benefits for the treatment of infections in orthopedics., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

A versatile template-assisted strategy for the preparation of monodispersed rattle-type hybrid nanospheres, encapsulating a movable Au nanocore in the hollow cavity of a hairy electroactive polymer shell (Au@air@PTEMA-g-P3HT hybrid nanorattles; PTEMA: poly(2-(thiophen-3-yl)ethyl methacrylate; P3HT: poly(3-hexylthiophene), was reported. The Au@silica core-shell nanoparticles, prepared by the modified Stöber sol-gel process on Au nanoparticle seeds, were used as templates for the synthesis of Au@silica@PTEMA core-double shell nanospheres. Subsequent oxidative graft polymerization of 3-hexylthiophene from the exterior surface of the Au@silica@PTEMA core-double shell nanospheres allowed the tailoring of surface functionality with electroactive P3HT brushes (Au@silica@PTEMA-g-P3HT nanospheres). The Au@air@ PTEMA-g-P3HT hybrid nanorattles were obtained after etching of the silica interlayer by HF. The as-prepared nanorattles were dispersed into an electrically insulating polystyrene matrix and for the first time used to fabricate nonvolatile memory devices. As a result, unique electrical behaviors, including insulator behavior, write-once-read-many-times and rewritable memory effects, and conductor behavior as well, were observed in the Al/Au@air@PTEMA-g-P3HT+PS/ITO (ITO: indium-tin oxide) sandwich thin-film devices., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Fe3O4 nanoparticles with surface hydroxyl groups (MNP-OH), prepared by the thermal decomposition of ferric oxalate pentahydrate in triethylene glycol, were grafted in situ with polyglycerol through the ring-opening polymerization of glycidol. By this method, hyperbranched polyglycerol-grafted Fe3O4 nanoparticles (HPG-grafted MNPs) can be obtained on an ultra-large scale of 50 g in a single reaction under laboratory conditions, and it is anticipated that the production of the HPG-grafted MNPs could be scaled up with the use of larger reaction vessels. The successful grafting of HPG onto the nanoparticles was confirmed by (1)H NMR and XPS analyses. The as-synthesized nanoparticles can be tuned from 8 to 24 nm in diameter by varying the reaction conditions. The size, morphology, and surface component of the nanoparticles were characterized by TEM, XPS, and XRD. The HPG-grafted MNPs are highly dispersible in aqueous media such as cell culture medium and serum. Since these magnetic nanoparticles possess desirable magnetic properties, controllable size, and can be produced by a facile inexpensive method, they can be potentially applied as a novel contrast agent for enhancing a MRI signal.

Titanium (Ti) has been functionalized with biomolecules for biomedical purposes. However, there is very limited information on the stability of such functionalities. Ti surface functionalized with carboxymethyl chitosan (CMCS) and bone morphogenetic protein 2 (BMP-2) has been reported to inhibit bacterial colonization while at the same time enhances osteoblast functions. In this work, three types of anchoring molecules, (3-aminopropyl) triethoxysilane (Silane), dopamine (DA), and polydopamine (PDA), were used for immobilizing the CMCS on Ti. The CMCS-modified surfaces were subjected to 70% ethanol treatment, autoclaving, and prolonged immersion in phosphate buffered saline (PBS). After the treatment procedures, the ability of the CMCS-modified substrates to inhibit colonization by Staphylococcus epidermidis (S. epidermidis) was assessed to evaluate the stability of the immobilized CMCS. The bacterial adhesion assays showed that the CMCS-DA- and CMCS-PDA-modified Ti remained stable after 70% ethanol treatment, autoclaving, and prolonged immersion in PBS, whereas the CMCS-Silane-modified Ti was less stable after autoclaving and prolonged immersion in PBS. The CMCS-DA- and CMCS-PDA-modified Ti substrates were functionalized with BMP-2 and used to support osteoblast growth. Evaluation of alkaline phosphatase (ALP) activity and calcium deposition from osteoblasts cultured on these substrates, which have been treated with 70% ethanol, or subjected to autoclaving, and prolonged immersion in PBS indicated that the immobilized BMP-2 on these surfaces retained its bioactivity., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Barnacle cement (BC) was utilized 'beneficially' as a surface anchor on stainless steel (SS) for coupling of functional polymer brushes via "click" reactions in both "grafting-to" and "grafting-from" processes. Ethylene sulfide (ES), propargyl carbonylimidazole (PPC) and azidoethyl carbonylimidazole (AEC) reacted with amine and/or hydroxyl groups in BC to introduce the corresponding thiol, alkyne, and azide groups on SS surfaces (SS-thiol, SS-alkyne, and SS-azide, respectively). Antifouling zwitterionic SS-PMPC surface was prepared by thiol-ene photopolymerization of 2-methacryloyloxyethyl phosphorylcholine (MPC) from the SS-thiol surface. Protein-resistant SS-PPEGMA and protein-adsorbing SS-PPFS surfaces were prepared by coupling of the respective azide-functionalized poly(poly(ethylene glycol)methyl ether methacrylate) (azido-PPEGMA) and poly(2,3,4,5,6-pentafluorostyrene) (azido-PPFS) polymer brushes in azide-alkyne "click" reaction. Antifouling alkyne-functionalized poly(N-hydroxyethyl acrylamide) (alkynyl-PHEAA) and antibacterial alkyne-functionalized poly(2-(methacryloyloxy)ethyl trimethylammonium chloride) (alkynyl-PMETA) polymer brushes were clicked on the SS-azide surface. Adsorption of bovine serum albumin and bacteria fouling of Gram-negative Escherichia coli ( E. coli ) and Gram-positive Staphylococcus epidermidis ( S. epidermidis ) were investigated on the polymer-functionalized SS surfaces. The versatile bioanchor and functional polymer brush coatings are stable in an abiotic aqueous environment for over a month.

Graphene oxide (GO) nanosheets can be functionalized with reactive pentafluorophenyl ester via esterification of the carboxylic groups. The resulting reactive GO nanosheets provide a versatile platform for grafting of amino-containing polymers or biomolecules via ester-amine coupling. Coupling of poly[(9,9-dioctylfluorene)-alt-(4-amino-phenylcarbazole)] (PFCz-NH(2) ), amino-terminated hyperbranched polyglycerol (HPG-NH(2) ), and lysozyme (Lyz) was illustrated. The Al/GO-g-PFCz/ITO sandwich thin-film device exhibits bistable electrical switching and rewritable memory effects. The GO-g-Lyz nanohybrids exhibit high bactericidal efficacy against S. aureus and E. coli, while the GO-g-HPG nanohybrids exhibit reduced cytotoxicity toward 3T3 fibroblasts., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Superparamagnetic nanoparticles grafted with hyperbranched polyglycerol (HPG) and conjugated with methotrexate (MTX) (MNP-g-HPG-MTX) were synthesized via a sol-gel reaction followed by thiol-ene click chemistry and esterification reaction. The successful grafting of MTX and HPG onto the nanoparticles was confirmed by X-ray photoelectron spectroscopy (XPS), Fourier transform infrared (FT-IR) spectroscopy, and UV-visible spectroscopy. The HPG-graft layer confers the magnetic nanoparticles with good dispersibility and stability in aqueous medium and macrophage-evasive property while the MTX acts as a chemotherapeutic drug as well as a tumor targeting ligand. The dose-dependent targeting and anticancer effect of the MNP-g-HPG-MTX nanoparticles were evaluated, and the results showed that depending on the amount of conjugated MTX and the concentration of the incubated nanoparticles, the uptake of MNP-g-HPG-MTX nanoparticles by human head and neck cancer (KB) cells can be eight times or more higher than those by 3T3 fibroblasts and RAW macrophages. As a result, the MNP-g-HPG-MTX nanoparticles are capable of killing ∼50% of the KB cells while at the same time exhibiting low cytotoxicity towards 3T3 fibroblasts and RAW macrophages. Thus, such nanoparticles can potentially be used as active targeting anticancer agents., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Dense and uniform polymer brush coatings were developed to combat marine biofouling. Nonionic hydrophilic, nonionic hydrophobic, cationic, anionic and zwitterionic polymer brush coatings were synthesized via surface-initiated atom transfer radical polymerization (SI-ATRP) of 2-hydroxyethyl methacrylate, 2,3,4,5,6-pentafluorostyrene, 2-(methacryloyloxy)ethyl trimethylammonium chloride, 4-styrenesulfonic acid sodium and N,N'-dimethyl-(methylmethacryloyl ethyl) ammonium propanesulfonate, respectively. The functionalized surfaces had different efficacies in preventing adsorption of bovine serum albumin (BSA), adhesion of the Gram-negative bacterium Pseudomonas sp. NCIMB 2021 and the Gram-positive Staphylococcus aureus, and settlement of cyprids of the barnacle Amphibalanus amphitrite (=Balanus amphitrite). The nonionic hydrophilic, anionic and zwitterionic polymer brushes resisted BSA adsorption during a 2 h exposure period. The nonionic hydrophilic, cationic and zwitterionic brushes exhibited resistance to bacterial fouling (24 h exposure) and cyprid settlement (24 and 48 h incubation). The hydrophobic brushes moderately reduced protein adsorption, and bacteria and cyprid settlement. The anionic brushes were least effective in preventing attachment of bacteria and barnacle cyprids. Thus, the best approach to combat biofouling involves a combination of nonionic hydrophilic and zwitterionic polymer brush coatings on material surfaces.

Metals are widely used in engineering as well as medical applications. However, their surfaces are easily colonized by bacteria that form biofilms. Among the numerous concerns with biofilm formation, biocorrosion is of particular importance in industry, because structural integrity may be compromised, leading to technical failures. In the food industry and medical field, biofilms also pose health risks. To inhibit bacterial colonization, the surfaces of metals can be coated with a polymeric layer which is antiadhesive and/or bactericidal. This article describes polymers that have these desired properties and the methodologies for immobilizing them on metal surfaces of relevance to the marine and medical fields. The focus is on polymer coatings that have a high degree of stability in aqueous medium and do not leach out. The efficacies of the different polymer coatings against bacteria commonly encountered in marine (Desulfovibrio desulfuricans) and medical applications (Staphylococcus aureus, Staphylococcus epidermidis and Escherichia coli) are demonstrated.

In vivo magnetic resonance imaging (MRI) tracking of macrophages plays an important role in monitoring and understanding numerous human diseases with high macrophage activity. In this work, superparamagnetic iron oxide nanoparticles (SPIONs) of ∼12 nm were surface-functionalized with poly(DL-lactic acid-co-malic acid) copolymer (PLMA) via a nanoprecipitation method. The r(1), r(2) and r(2) /r(1) values of the PLMA-SPIONs obtained at a magnetic field of 3 T were 0.38, 196 and 516 mM(-1) s(-1) , respectively. The high r(2)/r(1) ratio can be expected to provide enhanced MR contrast. The PLMA-SPIONs were readily taken in by macrophages and the high iron uptake was confirmed via Prussian Blue staining and quantified by inductively coupled plasma mass spectrometry (ICP-MS). No significant cytotoxicity was found even at a high nanoparticle loading of 67.7 pg Fe per cell. A linear relationship between R(2) and R2* values and the number of PLMA-SPIONs labeled cells was observed in vitro. As a result of the significantly higher R2* than R(2) effects, an in vitro detection threshold of about 2820 labeled cells was achieved with short labeling time and low nanoparticle concentration using a clinical 3 T MRI scanner. Thus, the PLMA-SPIONs can be potentially useful as magnetic resonance probes for targeting and tracking macrophages., (Copyright © 2011 John Wiley & Sons, Ltd.)

Ligand-mediated magnetic resonance (MR) contrast agents would be highly desirable for cancer diagnosis. In the present study, nanoparticles of Fe₃O₄ core with fluorescent SiO₂ shell were synthesized and grafted with hyperbranched polyglycerol (HPG-grafted Fe₃O₄@SiO₂ nanoparticles). These nanoparticles have a hydrodynamic diameter of 47.0 ± 4.0 nm, and are very stable in aqueous solution as well as in cell culture medium. Numerous surface hydroxyl groups of these nanoparticles were conjugated with folic acid by a thiol 'click' reaction. The successful covalent attachment of folic acid on the nanoparticles was confirmed by FTIR and XPS analyses. Both MR imaging and fluorescence microscopy show significant preferential uptake of the folic acid-conjugated polyglycerol-grafted Fe₃O₄@SiO₂ (FA-HPG-grafted Fe₃O₄@SiO₂) nanoparticles by human ovarian carcinoma cells (SKOV-3) as compared to macrophages and fibroblasts. Such nanoparticles can potentially be used to provide real-time imaging in ovarian cancer resection., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

To enhance the corrosion resistance of stainless steel (SS) and to impart its surface with antibacterial functionality for inhibiting biofilm formation and biocorrosion, well-defined inorganic-organic hybrid coatings, consisting of a polysilsesquioxane inner layer and quaternized poly(2-(dimethyamino)ethyl methacrylate) (P(DMAEMA)) outer blocks, were prepared via successive surface-initiated atom transfer radical polymerization (ATRP) of 3-(trimethoxysilyl)propyl methacrylate (TMSPMA) and 2-(dimethylamino)ethyl methacrylate (DMAEMA). The cross-linked P(TMASPMA), or polysilsesquioxane, inner layer provided a durable and resistant coating to electrolytes. The pendant tertiary amino groups of the P(DMAEMA) outer block were quaternized with alkyl halide to produce a high concentration of quaternary ammonium groups with biocidal functionality. The so-synthesized inorganic-organic hybrid coatings on the SS substrates exhibited good anticorrosion and antibacterial effects and inhibited biocorrosion induced by sulfate-reducing bacteria (SRB) in seawater media, as revealed by antibacterial assay and electrochemical analyses, and they are potentially useful to steel-based equipment under harsh industrial and marine environments.

To enhance the biocorrosion resistance of stainless steel (SS) and to impart its surface with bactericidal function for inhibiting bacterial adhesion and biofilm formation, well-defined functional polymer brushes were grafted via surface-initiated atom transfer radical polymerization (ATRP) from SS substrates. The trichlorosilane coupling agent, containing the alkyl halide ATRP initiator, was first immobilized on the hydroxylated SS (SS-OH) substrates for surface-initiated ATRP of (2-dimethylamino)ethyl methacrylate (DMAEMA). The tertiary amino groups of covalently immobilized DMAEMA polymer or P(DMAEMA), brushes on the SS substrates were quaternized with benzyl halide to produce the biocidal functionality. Alternatively, covalent coupling of viologen moieties to the tertiary amino groups of P(DMAEMA) brushes on the SS surface resulted in an increase in surface concentration of quaternary ammonium groups, accompanied by substantially enhanced antibacterial and anticorrosion capabilities against Desulfovibrio desulfuricans in anaerobic seawater, as revealed by antibacterial assay and electrochemical studies. With the inherent advantages of high corrosion resistance of SS, and the good antibacterial and anticorrosion capabilities of the viologen-quaternized P(DMAEMA) brushes, the functionalized SS is potentially useful in harsh seawater environments and for desalination plants., (Copyright 2009 Wiley Periodicals, Inc.)

A novel surface modification technique was developed to provide a copper nickel alloy (M) surface with bactericidal and anticorrosion properties for inhibiting biocorrosion. 4-(chloromethyl)-phenyl tricholorosilane (CTS) was first coupled to the hydroxylated alloy surface to form a compact silane layer, as well as to confer the surface with chloromethyl functional groups. The latter allowed the coupling of 4-vinylpyridine (4VP) to generate the M-CTS-4VP surface with biocidal functionality. Subsequent surface graft polymerization of 4VP, in the presence of benzoyl peroxide (BPO) initiator, from the M-CTS-4VP surface produced the poly(4-vinylpyridine) (P(4VP)) grafted surface, or the M-CTS-P(4VP) surface. The pyridine nitrogen moieties on the M-CTS-P(4VP) surface were quaternized with hexylbromide to produce a high concentration of quaternary ammonium groups. Each surface functionalization step was ascertained by X-ray photoelectron spectroscopy (XPS) and static water contact angle measurements. The alloy with surface-quaternized pyridinium cation groups (N+) exhibited good bactericidal efficiency in a Desulfovibrio desulfuricans-inoculated seawater-based modified Barr's medium, as indicated by viable cell counts and fluorescence microscopy (FM) images of the surface. The anticorrosion capability of the organic layers was verified by the polarization curve and electrochemical impedance spectroscopy (EIS) measurements. In comparison, the pristine (surface hydroxylated) Cu-Ni alloy was found to be readily susceptible to biocorrosion under the same environment.

A simple one-pot process was developed for the covalent immobilization of atom transfer radical polymerization (ATRP) initiators with quaternized triethylamine moieties on the carboxyl-functionalized multiwalled carbon nanotubes (MWCNTs). The initiator-coupled MWCNTs exhibited good dispersion in water and could be used directly to prepare water-dispersion of polymer-MWCNT hybrids, such as stimuli-responsive poly(N-isopropyl acrylamide)-MWCNT hybrids, via surface-initiated ATRP of N-isopropylacrylamide in an aqueous medium. The present one-pot synthesis of the ATRP initiator-immobilized MWCNTs with good dispersion in water provides an alternative route to the direct preparation of water-soluble polymer-MWCNT hybrids in aqueous media.

Poly(N-isopropylacrylamide) (PIPAAm) has been demonstrated as an effective thermoresponsive polymer for non-invasive cell regeneration/recovery. However, little is known about the intricate relationship between the biophysical response of cells and physiochemical properties of PIPAAm during cell recovery. In this study, the de-adhesion kinetics of smooth muscle cell (SMC) on PIPAAm surfaces is probed with unique biophysical techniques. Water-immersion atomic force microscope (AFM) first showed that the nanotopology of PIPAAm surfaces is dependent on the polymerization time and collagen coating. It is found that the initial rate of cell de-adhesion increases with the increase in polymerization time. Moreover, the degree of cell deformation (a/R) and average adhesion energy are reduced with the increase of grafted PIPAAm density during 40min of cell de-adhesion. It has been shown that collagen coating regulates cell adhesion on biomaterial surface. Interestingly, lower collagen density on PIPAAm leads to higher adhesion energy per cell during the initial 20min compared with as-prepared PIPAAm, while the initial rate of cell de-adhesion remains unchanged. In contrast, higher collagen density leads to 50% reduction in the initial rate of cell de-adhesion and higher adhesion energy per cell during the entire 90min. Furthermore, immunostaining of actin provides supporting evidence that the de-adhesion kinetics is correlated with the cytoskeleton transformation during cell de-adhesion below the lower solution critical temperature (LCST).

Stimuli-responsive polymers are of crucial importance in the design of smart biomaterials. The thermo-responsive triblock copolymers of polycaprolactone (PCL) and poly( N-isopropylacrylamide) (P(NIPAAm)), or P(NIPAAm)- b-PCL- b- P(NIPAAm) copolymers, were synthesized in this work via atom transfer radical polymerization (ATRP). The P(NIPAAm)- b-PCL- b-P(NIPAAm) copolymers were cast by phase inversion in water into porous membranes with well-defined and uniformly distributed pores. The P(NIPAAm) content in the P(NIPAAm)- b-PCL- b- P(NIPAAm) copolymers and the temperature of the aqueous medium for phase inversion could be used to control the pore size and porosity of the membranes. The thermo-responsive characteristics of the membranes were illustrated in the controlled water uptake and temperature-dependent glucose transport through the membranes. These temperature-sensitive membranes with controllable morphology have potential applications in biomedical engineering, drug delivery, and tissue engineering.

Poly(poly(ethyleneglycol) monomethacrylate) (P(PEGMA))-grafted magnetic nanoparticles (MNPs) were successfully prepared via a solvent-free atom transfer radical polymerization (ATRP) method. The macroinitiators were immobilized on the surface of 6.4+/-0.8 nm Fe(3)O(4) nanoparticles via effective ligand exchange of oleic acid with 3-chloropropionic acid (CPA), which rendered the nanoparticles soluble in the PEGMA monomer. The so-obtained P(PEGMA)-grafted MNPs have a uniform hydrodynamic particle size of 36.0+/-1.2 nm. The successful grafting of P(PEGMA) on the MNP surface was ascertained from FTIR and XPS analyses. The uptake of the MNPs by macrophage cells is reduced by two-orders of magnitude to <2 pg Fe/cell after surface grafting with P(PEGMA). Furthermore, the morphology and viability of the macrophage cells cultured in a medium containing 0.2 mg/mL of P(PEGMA)-grafted MNPs were found similar to those of cells cultured without nanoparticles, indicating an absence of significant cytotoxicity effects. T(2)-weighted magnetic resonance imaging (MRI) of P(PEGMA)-grafted MNPs showed that the magnetic resonance signal is enhanced significantly with increasing nanoparticle concentration in water. The R(1) and R(2) values per millimole Fe, and R(2)/R(1) value of the P(PEGMA)-grafted MNPs were calculated to be 8.8 mm(-1)s(-1), 140 mm(-1)s(-1), and 16, respectively. These results indicate that the P(PEGMA)-grafted MNPs have great potential for application in MRI of specific biotargets.

The present study deals with the synthesis and characterization of tamoxifen-loaded magnetite/poly(l-lactic acid) composite nanoparticles (TMCN), and their in vitro anti-cancer activity against MCF-7 breast cancer cells. The composite nanoparticles with an average size of approximately 200 nm, were synthesized via a solvent evaporation/extraction technique in an oil/water emulsion. The superparamagnetic property (saturation magnetization value of approximately 7 emu/g) of the TMCN is provided by Fe(3)O(4) nanoparticles of approximately 6 nm encapsulated in the poly(l-lactic acid) matrix. The encapsulation efficiency of the Fe(3)O(4) and tamoxifen as a function of the concentration in the organic phase was investigated. The uptake of TMCN and tamoxifen by MCF-7 was estimated from the intracellular iron concentration. After 4h incubation of MCF-7 with TMCN, significant changes in the cell morphology were discernible from phase contrast microscopy. Cytotoxicity assay shows that while the Fe(3)O(4)-loaded poly(l-lactic acid) composite nanoparticles exhibit no significant cytotoxicity against MCF-7, approximately 80% of the these cells were killed after incubation for 4 days with TMCN.

Conductive polypyrrole-palladium (PPy-Pd) composite nanospheres of about 50 nm in diameter, containing dispersed Pd metal nanoparticles of about 2-4 nm in size, were prepared in a 1-step oxidative polymerization of pyrrole by Pd(NO3)2. Pyrrole was oxidized by Pd(NO3)2 in an inverse microemulsion polymerization system, yielding PPy nanospheres and elemental Pd nanoparticles simultaneously. Palladium nanoparticles were uniformly dispersed in the nanospheres of PPy chains. The latter also exhibited an enhanced effective conjugation. The chemical composition of the PPy-Pd composite nanospheres was characterized by X-ray photoelectron spectroscopy and FTIR spectroscopy. The crystalline structure of the Pd nanoparticles was deduced from X-ray diffraction patterns. The morphology of the composites was revealed by scanning and transmission electron microscopy.

Well-defined poly((2-dimethyl amino)ethyl methacrylate-co-2-hydroxyethyl methacrylate)-b-poly(N-isopropylacrylamide)-b-poly((2-dimethyl amino)ethyl methacrylate-co-2-hydroxyethyl methacrylate), or P(DMAEMA-co-HEMA)-b-P(NIPAAm)-b-P(DMAEMA-co-HEMA), triblock copolymers were synthesized by consecutive atom transfer radical polymerizations (ATRPs), using ethylene glycol di-2-bromoisobutyrate (Br-EG-Br) as the starting ATRP initiator. The hydroxyl groups of the incorporated HEMA units were used as crosslinking sites for the preparation of smart hydrogels. The so-prepared hydrogels exhibited both temperature- and pH-sensitive behavior derived, respectively, and independently, from the P(NIPAAm) blocks and P(DMAEMA) units, in the crosslinked matrices. The hydrogels exhibited a lower critical solution temperature (LCST) of 31-32 degrees C in aqueous media of pH 1-7, not unlike that of the P(NIPAAm) homopolymer. The swelling ratios and swelling/deswelling kinetics of the hydrogels depended strongly on pH and temperature of the medium. The copolymers were characterized by gel-permeation chromatography, X-ray photoelectron spectroscopy (XPS), Fourier-transform infrared (FTIR) spectroscopy, and (1)H nuclear magnetic resonance ((1)H NMR) spectroscopy. The resultant stimuli-responsive hydrogels were characterized by differential scanning calorimetry (DSC). These stimuli-responsive hydrogels will have potential applications in biomedical areas, such as tissue engineering and drug delivery.

A new method to PEGylate magnetic nanoparticles with a dense layer of poly(poly(ethylene glycol) monomethacrylate) (P(PEGMA)) by surface-initiated atom transfer radical polymerization (ATRP) is reported. In this approach, an initiator for ATRP was first immobilized onto the magnetic nanoparticle surface, and then P(PEGMA) was grafted onto the surface of magnetic nanoparticle via copper-mediated ATRP. The modified nanoparticles were subjected to detailed characterization using FTIR, XPS, and TGA. The P(PEGMA)-immobilized nanoparticles dispersed well in aqueous media. The saturation magnetization values of the P(PEGMA)-immobilized nanoparticles were 19 emu/g and 11 emu/g after 2 and 4 h polymerization respectively, compared to 52 emu/g for the pristine magnetic nanoparticles. The response of macrophage cells to pristine and P(PEGMA)-immobilized nanoparticles was compared. The results showed that the macrophage cells are very effective in cleaning up the pristine magnetic nanoparticles. With the P(PEGMA)-immobilized nanoparticles, the amount of nanoparticles internalized into the cells is greatly reduced to <2 pg/cell over a 5 day period. With this amount of nanoparticles uptake, no significant cytotoxicity effects were observed.

Bulk modification of polypyrrole (PPY) with poly(vinyl alcohol) (PVA) was carried out by the electropolymerization of pyrrole in the presence of PVA in the reaction solution, with tetraethylammonium perchlorate (TEAP) as the electrolyte. The surface morphology of the as-synthesized PPY-TEAP-PVA film was investigated using scanning electron microscopy, and the film was further characterized using X-ray photoelectron spectroscopy, electrical conductivity, the water contact angle, and BET surface area measurements. The PPY-TEAP-PVA composite is electrically conductive, hydrophilic, and microporous with a high surface area. Its potential as a biomaterial was investigated with respect to its blood compatibility and function as a substrate for biosensor fabrication and cell culture. The presence of PVA in the film attenuates blood protein adsorption, and the porous nature of the PPY-TEAP-PVA film results in a 10-fold increase in the amount of glucose oxidase covalently immobilized on the film over that on a nonporous PPY film. PC12 cell attachment and growth on the PPY-TEAP-PVA film was also shown to be enhanced compared with that on tissue culture polystyrene. The attached cells proliferated and formed a monolayer on the film surface after 48 h of seeding.

Two brush-type amphiphilic diblock copolymers, poly(poly(ethylene glycol)methyl ether methacrylate-block-polystyrene) (P(PEGMA)-b-PS) and poly(glycidyl methacrylate)-block-poly(poly(ethylene glycol)methyl ether methacrylate) (P(GMA)-b-P(PEGMA)) were synthesized, respectively, via consecutive atom-transfer radical polymerizations (ATRPs) and reversible addition-fragmentation chain-transfer (RAFT) polymerizations. The diblock copolymers were characterized by gel permeation chromatography (GPC), (1)H nuclear magnetic resonance (NMR) spectroscopy, and FT-IR spectroscopy. The aggregation behavior of the two amphiphilic diblock copolymers in water was also studied. Scanning electron and transmission electron microscopic images revealed that spherical micelles (40-80 nm in diameter) from self-assembly of the P(PEGMA)-b-PS copolymers and wormlike micelles (60-120 nm in length and 20-30 nm in diameter) from self-assembly of the P(GMA)-b-P(PEGMA) copolymers were prevalent. The spherical P(PEGMA)-b-PS micelles could self-assemble gradually into giant aggregates of several micrometers in diameter.

A surface modification technique was developed for the covalent immobilization of poly(vinyl alcohol) (PVA)-heparin hydrogel onto electrically conductive polypyrrole (PPY) film with the objective of achieving controlled release of heparin. First, aldehyde groups were introduced onto PPY film through poly(ethylene glycol) monomethacrylate graft copolymerization and subsequent oxidation in acetic anhydride and dimethyl sulfoxide mixture. Then, the prepared PVA-heparin hydrogel was cast onto the PPY film and covalently immobilized to the film through the reaction between the aldehyde groups on the PPY film and the hydroxyl groups of PVA. X-ray photoelectron spectroscopy was used to characterize the surface-modified film after each stage. The strong attachment of the PVA-heparin layer on the PPY film was confirmed by peel test and scanning electron microscopy. The release behavior of heparin from the substrate with and without electrical stimulation was studied and the experimental results showed that the heparin release rate from the prepared substrate using an electric current of 3.5 mA is twofold higher than that without current.

Surface modification of poly(tetrafluoroethylene) (PTFE) films by well-defined comb copolymer brushes was carried out. Peroxide initiators were generated directly on the PTFE film surface via radio frequency Ar plasma pretreatment, followed by air exposure. Poly(glycidyl methacrylate) (PGMA) brushes were first prepared by surface-initiated reversible addition-fragmentation chain transfer polymerization from the peroxide initiators on the PTFE surface in the presence of a chain transfer agent. Kinetics study revealed a linear increase in the graft concentration of PGMA with the reaction time, indicating that the chain growth from the surface was consistent with a "controlled" or "living" process. alpha-Bromoester moieties were attached to the grafted PGMA by reaction of the epoxide groups with 2-bromo-2-methylpropionic acid. The comb copolymer brushes were subsequently prepared via surface-initiated atom transfer radical polymerization of two hydrophilic vinyl monomers, including poly(ethylene glycol) methyl ether methacrylate and sodium salt of 4-styrenesulfonic acid. The chemical composition of the modified PTFE surfaces was characterized by X-ray photoelectron spectroscopy.

Surface-initiated atom-transfer radical polymerization (ATRP) of poly(ethylene glycol) monomethacrylate (PEGMA) was carried out on the hydrogen-terminated Si(100) substrates with surface-tethered alpha-bromoester initiator. Kinetic studies confirmed an approximately linear increase in polymer film thickness with reaction time, indicating that chain growth from the surface was a controlled "living" process. The "living" character of the surface-grafted PEGMA chains was further ascertained by the subsequent extension of these graft chains, and thus the graft layer. Well-defined polymer brushes of near 100 nm in thickness were grafted on the Si(100) surface in 8 h under ambient temperature in an aqueous medium. The hydroxyl end groups of the poly(ethylene glycol) (PEG) side chains of the grafted PEGMA polymer were derivatized into various functional groups, including chloride, amine, aldehyde, and carboxylic acid groups. The surface-functionalized silicon substrates were characterized by reflectance FT-IR spectroscopy and X-ray photoelectron spectroscopy (XPS). Covalent attachment and derivatization of the well-defined PEGMA polymer brushes can broaden considerably the functionality of single-crystal silicon surfaces.

Electrically conductive polypyrrole (PPY) was surface functionalized with hyaluronic acid (HA) and sulfated hyaluronic acid (SHA) to improve its surface biocompatibility. The immobilization of HA on the PPY film was facilitated by the use of a cross-linker having the appropriate functional groups. The biological activity of the HA functionalized PPY film was assessed by means of an in vitro PC12 cell culture. The cell attachment on different substrates was studied and determined by bicinchoninic acid protein analysis. Cell attachment on the HA functionalized PPY film surface was significantly enhanced in the presence of nerve growth factor. The SHA functionalized PPY film was obtained by the sulfonation of the immobilized HA using pyridinesulfonate. The retention of the biological activity of the immobilized HA after sulfonation was evaluated by the in vitro assessment of the plasma recalcification time (PRT) and platelet adhesion on the substrate. The PRT observed from the SHA functionalized PPY film was significantly prolonged compared with the HA functionalized PPY. Some reduction of platelet adhesion was observed for the SHA functionalized PPY film, compared with that of the HA functionalized PPY film.

Controlled grafting of well-defined epoxide polymer brushes on the hydrogen-terminated Si(100) substrates (Si-H substrates) was carried out via the surface-initiated atom-transfer radical polymerization (ATRP) at room temperature. Thus, glycidyl methacrylate (GMA) polymer brushes were prepared by ATRP from the alpha-bromoester functionalized Si-H surface. Kinetic studies revealed a linear increase in GMA polymer (PGMA) film thickness with reaction time, indicating that chain growth from the surface was a controlled "living" process. The graft polymerization proceeded more rapidly in the dimethylformamide/water (DMF/H(2)O) mixed solvent medium than in DMF, leading to much thicker PGMA growth on the silicon surface in the former medium. The chemical composition of the GMA graft-polymerized silicon (Si-g-PGMA) surfaces were characterized by X-ray photoelectron spectroscopy (XPS). The fact that the epoxide functional groups of the grafted PGMA were preserved quantitatively was revealed in the reaction with ethylenediamine. The "living" character of the PGMA chain end was further ascertained by the subsequent growth of a poly(pentafluorostyrene) (PFS) block from the Si-g-PGMA surface, using the PGMA brushes as the macroinitiators.

The surface functionalization of an electrically conductive polypyrrole film (PPY) with a viologen, (N-(2-carboxyl-ethyl)-N'-(4-vinyl-benzyl)-4,4'-bipyridinium dichloride, or CVV) for the covalent immobilization of glucose oxidase (GOD) has been carried out. The viologen was first synthesized and graft polymerized on PPY film. It then served as an anchor via its carboxyl groups for the covalent immobilization of GOD. The surface composition of the as-functionalized substrates was characterized by X-ray photoelectron spectroscopy (XPS). The effects of the CVV monomer concentration on the CVV-graft polymer concentration and the amount of GOD immobilized on the surface were investigated. The activity of the immobilized GOD was compared with that of free GOD and the kinetic effects were also obtained. The cyclic voltammetric (CV) response of the GOD-functionalized PPY substrates was studied in a phosphate buffer solution under an argon atmosphere. The CV results support the mechanism in which CVV acts as a mediator to transfer electron between the electrode and enzyme, and hence regenerating the enzyme in the enzymatic reaction with glucose. High sensitivity and linear response of the enzyme electrode was observed with glucose concentration ranging from 0 to 20 mM.

A surface modification technique was developed for the covalent immobilization of heparin onto electrically conductive polypyrrole (PPY) film. The PPY film was first graft copolymerized with poly(ethylene glycol) methacrylate (PEGMA) and then activated with cyanuric chloride (CC). Heparin was then immobilized onto the film through the reaction between the chloride groups of CC and the amine and/or hydroxyl groups of heparin. X-ray photoelectron spectroscopy (XPS) was used to characterize the surface-modified film after each stage. The biocompatibility of the surface-modified PPY was evaluated using plasma recalcification time (PRT) and platelet adhesion. After surface modification, the film had improved wettability while retaining significant electrical conductivity. With immobilized heparin, platelet adhesion and platelet activation on PPY film was significantly suppressed, and the PRT was significantly prolonged. Electrical stimulation also plays a positive role in decreasing platelet adhesion and increasing PRT on pristine and surface-modified PPY films., (Copyright 2003 Wiley Periodicals, Inc.)

A surface modification technique was developed for the functionalization of polypyrrole (PPY) film with glucose oxidase (GOD) and viologen moieties. The PPY film was first graft copolymerized with acrylic acid (AAc) and GOD was then covalently immobilized through the amide linkage formation between the amino groups of the GOD and the carboxyl groups of the grafted AAc polymer chains in the presence of a water-soluble carbodiimide. Viologen moieties could also be attached to the PPY film via graft-copolymerization of vinyl benzyl chloride with the PPY film surface followed by reaction with 4,4'-bipyridine and alpha,alpha'-dichloro-p-xylene. X-ray photoelectron spectroscopy (XPS) was used to characterize the PPY films after each surface modification step. Increasing the AAc graft concentration would allow a greater amount of GOD to be immobilized but this would decrease the electrical conductivity of the PPY film. The activity of the immobilized GOD was compared with that of free GOD and the kinetic effects were also studied. The immobilized GOD was found to be less sensitive to temperature deactivation as compared to the free GOD. The results showed that the covalent immobilization technique offers advantages over the technique involving the entrapment of GOD in PPY films during electropolymerization. The presence of viologen in the vicinity of the immobilized GOD also enabled the GOD-catalyzed oxidation of glucose to proceed under UV irradiation in the absence of O(2)., (Copyright 2002 Elsevier Science B.V.)