Synthesis and characterization of a microsphere‐based coating for textiles with potential as an in situ bioactive delivery system

Proteinaceous microspheres have a wide range of biomedical applications, including their use as drug delivery systems. On the other hand, bioactive and antimicrobial textiles are promising substrates for medical care, in particular, as wound‐dressings. This work relates the development of a new process for the functionalization of textiles through the simultaneous formation and linkage of protein‐based microspheres onto textile fibers by sonochemical techniques. The microspheres developed by this process possess antimicrobial properties by themselves, but other may be incorporated by the encapsulation of various pharmaceutical formulations. This new type of microspheres and particularly their fixation onto textile materials encourage the development of textiles that can be used as delivery systems in a simple, fast, and non‐toxic process. Here it is reported the production of microspheres with a combination of bovine serum albumin (BSA), L ‐Cysteine (L ‐Cys), and n‐dodecane, using the ultrasound technology. The size distribution and morphology of the microspheres was determined as a function of several parameters such as irradiation time and BSA and L ‐Cys concentrations. The produced microspheres were analyzed using a laser light scattering size analyzer, an optical microscope and a scanning electron microscope. The new coating of BSA + L ‐Cys microspheres revealed a high stability and excellent antibacterial properties being a promising alternative to design textile‐based bioactive delivery systems with potential application in the development of textile‐based wound‐dressings. Copyright © 2011 John Wiley & Sons, Ltd.     

A Preloaded Amorphous Calcium Carbonate/Doxorubicin@Silica Nanoreactor for pH‐Responsive Delivery of an Anticancer Drug

Biomedical applications of nontoxic amorphous calcium carbonate (ACC) nanoparticles have mainly been restricted because of their aqueous instability. To improve their stability in physiological environments while retaining their pH‐responsiveness, a novel nanoreactor of ACC–doxorubicin (DOX)@silica was developed for drug delivery for use in cancer therapy. As a result of its rationally engineered structure, this nanoreactor maintains a low drug leakage in physiological and lysosomal/endosomal environments, and responds specifically to pH 6.5 to release the drug. This unique ACC–DOX@silica nanoreactor releases DOX precisely in the weakly acidic microenvironment of cancer cells and results in efficient cell death, thus showing its great potential as a desirable chemotherapeutic nanosystem for cancer therapy.     

Dual‐responsive crosslinked micelles of a multifunctional graft copolymer for drug delivery applications

A novel multifunctional amphiphilic graft copolymer has been synthesized consisting of a biodegradable poly(l ‐aspartic acid) backbone that was decorated by water‐soluble poly(ethylene glycol) (PEG) and pH‐responsive poly(N,N‐diethylaminoethyl methacrylate) (PDEAEMA) side‐chains as well as thiol pendant groups. This graft copolymer together with doxorubicin (DOX) formed micelles in water at pH = 10.0 with PDEAEMA and DOX acting as the core and PEG serving as the micellar corona. Upon oxidation, the thiol groups dimerized to form disulfide bonds, thus “locking in” the micellar structure. These crosslinked micelles expanded as the pH was decreased from 7.4 to 5.0 or upon the addition, at pH = 7.4, of glutathione (GSH), a thiol‐containing oligopeptide that is present in cancerous cells and cleaves disulfide bonds. At pH = 5.0, GSH addition triggered the disassembly of the micelles. The expansion and disassembly of the micelles have been determined via in vitro experiments to evaluate their DOX release behavior. More importantly, the graft copolymer micelles could enter cells by means of endocytosis and deliver DOX to the nuclei of ovarian cancer BEL‐7402 cells. Thus, this polymer and its micelles are promising candidates for drug delivery applications. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017 , 55, 1536–1546     

Synthesis of a Magnetic Carnation-like Hydroxyapatite/Basic Calcium Carbonate Nanocomposite and Its Adsorption Behaviors for Lead Ions in Water

Calcium-enriched compounds have great potential in the treatment of heavy-metal contaminated wastewater. Preparing stable basic calcium carbonate (BCC), which is a calcium-enriched compound, and applying it in practice is a great challenge. This work investigated the formation process of hierarchical hydroxyapatite (HAP)/BCC nanocomposites and their adsorption behaviors regarding lead ions (Pb²⁺). The morphology of the HAP/BCC nanocomposite was controlled by the addition of monododecyl phosphate (MDP). The carnation-like HAP/BCC nanocomposite was achieved with the addition of 30 g of MDP. The carnation-like HAP/BCC nanocomposite had a high Pb²⁺ adsorption capacity of 860 mg g⁻¹. The pseudo-second-order and Freundlich model simulation results indicated that the adsorptions of Pb²⁺ on the nanocomposites belonged to the chemisorption and multilayer adsorption processes. The main effective adsorption components for the nanocomposites were calcium-enriched HAP and BCC. Through the Ca²⁺ ions exchanging with Pb²⁺, the HAP and BCC phases were converted to hydroxyl-pyromorphite (Pb-HAP) and hydrocerussite (Pb₃(CO₃)₂(OH)₂), respectively. The carnation-like HAP/BCC nanocomposite has great potential in the treatment of heavy metal ions. This facile method provides a new method for preparing a stable HAP/BCC nanocomposite and applying it in practice.     

Calcium Phosphate Hybrid Nanoparticles: Self‐Assembly Formation,Characterization, and Application as an Anticancer Drug Nanocarrier

Calcium phosphate hybrid nanoparticles (CaP‐HNPs) have been synthesized in aqueous solution through self‐assembly by using two oppositely charged polyelectrolytes (poly(diallyldimethylammonium chloride) (PDADMAC) and poly(acrylate sodium) (PAS)) as dual templates. First, the PAS/Ca²⁺ and PDADMAC/PO₄^3? complexes form through electrostatic interactions and then two complexes self‐assemble into CaP‐HNPs after mixing them together. The as‐prepared CaP‐HNPs exhibit a spherical morphology with a narrow size distribution, good dispersibility, and high colloidal stability in water. The CaP‐HNPs are explored as a nanocarrier for the anticancer drug docetaxel (Dtxl). The CaP‐HNPs show excellent biocompatibility, high drug‐loading capacity, pH‐sensitive drug‐release behavior, and high anticancer effect after being loaded with Dtxl. Therefore, the as‐prepared CaP‐HNPs are promising drug nanocarriers for cancer therapy.     

Molecular engineering of sensitizers for dye‐sensitized solar cell applications

Dye‐sensitized solar cells (DSSCs) have attracted considerable attention in recent years as they offer the possibility of low‐cost conversion of photovoltaic energy. This account focuses on recent advances in molecular design and technological aspects of sensitizers based on metal complexes, metal‐free organics and tetrapyrrolic compounds which include porphyrins, phthalocyanines as well as corroles. Special attention has been paid to the design principles of these dyes, and co‐sensitization, an emerging technique to extend the absorption range, is also discussed as a way to improve the performance of the device. This account also focuses on recent advances of efficient ruthenium sensitizers as well as other metal complexes and their applications in DSSCs. Recent developments in the area of metal‐free organic and tetrapyrrolic sensitizers are also discussed. DOI 10.1002/tcr.201100044     

Studies of a cobalt(III) complex of the MMP inhibitor marimastat: a potential hypoxia-activated prodrug

We report a potential means of selectively delivering matrix metalloproteinase (MMP) inhibitors to target tumour sites by use of a bioreductively activated Co(III) carrier system. The carrier, comprising a Co(III) complex of the tripodal ligand tris(methylpyridyl)amine (tpa), was investigated with the antimetastatic MMP inhibitor marimastat (mmstH(2)). The X-ray crystal structure of [Co(mmst)(tpa)]ClO(4) x 4H(2)O was determined and two-dimensional NMR revealed the existence of two isomeric forms of the complex in solution. Electrochemical analysis showed that the reduction potential of the complex is suitable for it to be bioreductively activated at hypoxic tumour sites. In vitro assays confirmed the stability of the prodrug in solution prior to reduction and revealed very low cytotoxicity against A2780 cells. In vivo testing in mice showed a higher level of tumour-growth inhibition by the complex than by free marimastat. Both free marimastat and and its Co(III) complex increased metastasis in the model used, with the complex significantly more active.     

A self-powered "sense-act-treat" system that is based on a biofuel cell and controlled by boolean logic

Bio-logic-al: an autonomous, integrated "sense-act-treat" system that is based on an enzymatic biofuel cell has been developed. The system couples a biocomputing logic-detection method with a drug-release system to provide a logic-activated therapeutic intervention in response to a simulated abnormal physiological state, without the need for an external power source, control electronics, or microelectromechanical actuators.     

Side chain impacts on pH‐ and thermo‐responsiveness of tertiary amine functionalized polypeptides

The systemic investigation of the structural impacts of side chains on the pH‐ and thermo‐responsiveness of tertiary amine functionalized poly(l ‐glutamate)s (TA‐PGs) was carried out. The TA‐PGs polymers were effectively synthesized by Cu(I)‐catalyzed azide‐alkyne cycloaddition click reaction of azido tertiary amines with poly(γ‐propargyl‐l ‐glutamate) (PPLG). Turbimetric measurements were performed to characterize the pH‐ and temperature‐induced phase transition of TA‐PGs in aqueous solution, which suggested a structural dependence of the properties on the N‐substituted groups and the “linkers” between 1,2,3‐triazole ring and the tertiary amine groups in the side chains. In detail, the pH responsive properties of TA‐PGs were basically determined by the hydrophobicity of the N‐substituted groups in the side chains and the pH transition point (pH_t) decreased as the increasing hydrophobicity of the N‐substituted groups, while the temperature‐responsiveness of TA‐PGs were affected by either the N‐substituted groups or the “linkers.” TA‐PGs with a moderate N‐substituted amine group (e.g., DEA, PR, and PD) or a branched “linker” (e.g., iso‐propylene and 2‐methylpropylene group) were more likely to express the LCST‐type phase transition tuned by pH variation. These structure–property relationships revealed in this study would help to develop the applications of TA‐PGs in smart drug delivery systems. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 671–679     

Assembly and application advancement of organic‐functionalized graphene‐based materials: A review

Owing to the remarkable physicochemical properties such as hydrophobicity, conductivity, elasticity, and light weight, graphene‐based materials have emerged as one of the most appealing carbon allotropes in materials science and chemical engineering. Unfortunately, pristine graphene materials lack functional groups for further modification, severely hindering their practical applications. To render graphene materials with special characters for different applications, graphene oxide or reduced graphene oxide has been functionalized with different organic agents and assembled together, via covalent binding and various noncovalent forces such as π–π interaction, electrostatic interaction, and hydrogen bonding. In this review, we briefly discuss the state‐of‐the‐art synthetic strategies and properties of organic‐functionalized graphene‐based materials, and then, present the prospective applications of organic‐functionalized graphene‐based materials in sample preparation.     

Synthesis and metal complexation of dihydroxyphosphino‐functionalized crosslinked styrene/maleic anhydride copolymers

Crosslinked styrene (St)/maleic anhydride (MA) copolymers were synthesized, hydrolyzed with dicarboxylic acid, and converted to bear dihydroxyphosphino functionalities. The St–MA copolymers were prepared by azobisisobutyronitrile‐initiated polymerization in toluene at 90 °C in the presence of 2, 10, or 20% divinylbenzene crosslinker. The MA moiety was hydrolyzed into dicarboxylic acid to improve the hydrophilicity of the copolymers. The phenyl ring of St was phosphorylated with phosphorus trichloride in the presence of aluminum chloride and then hydrolyzed and oxidized with nitric acid at room temperature. The structures of the hydrolyzed and dihydroxyphosphino‐functionalized copolymers were confirmed by Fourier transform infrared spectroscopy and elemental analysis. The complexation behavior of these functionalized copolymers toward metal ions in 25 ppm aqueous solutions was observed over time periods of up to 7 h. The adsorption toward Pb(+2) was highest, followed by those of Cu(+2), Cr(+3), and Ni(+2). On the dihydroxyphosphino‐functionalized St–MA (20% divinylbenzene) copolymer, the adsorption of Pb(+2) showed a linear relationship with the concentrations and fit the Langmuir isotherm. The kinetics of Pb(+2) adsorption on this dihydroxyphosphino‐functionalized copolymer also fit the rate equation of the moving boundary model, t = [1 ? 3(1 ? X)^2/3 + 2(1 ? X)], where X is the fractional conversion. The metal‐ion adsorption kinetics of this copolymer appeared to be particle diffusion control, in which the moving boundary advanced from the surface toward the center. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 92–101, 2004     

Construction of Hyaluronic Acid-Covered Hierarchically Porous MIL-nanoMOF for Loading and Controlled Release of Doxorubicin

The porous nano-sized metal–organic framework (nanoMOF) and its proper surface modification could greatly promote the drug loading capability and introduce biocompatibility, biodegradability, and targeting functions into nano-drug delivery systems. Herein, the HACD@ADA-PA/MIL-101_NH₂ (Fe)-P nanoparticle was successfully fabricated through supramolecular and coordination interactions from three building blocks, including hierarchically porous MIL-101_NH₂ (Fe)-P nanoMOF, phosphite-modified adamantane (ADA-PA), and β-cyclodextrin (β-CD)-modified hyaluronic acid (HACD). The obtained HACD@ADA-PA/MIL-101_NH₂ (Fe)-P nanoparticle was nano-sized and highly stable in physiological fluids. The porous structure of HACD@ADA-PA/MIL-101_NH₂ (Fe)-P nanoparticle could effectively load the commercial chemotherapeutic drug doxorubicin (DOX) with an encapsulation rate of 41.20 % and a loading rate of 48.84 %. The obtained drug-loaded HACD@ADA-PA/MIL-101_NH₂ (Fe)-P@DOX nanoparticle was pH-sensitive and relatively stable at neutral condition (pH 7.2) but could release DOX in a controlled way in subacid solution at pH 5.7. The simulated in vitro DOX release experiment signified that the HACD@ADA-PA/MIL-101_NH₂ (Fe)-P@DOX nanoparticle could realize the controlled release of DOX in tumor issues.     

Chemical control of stem cell fate and developmental potential

Potential applications of stem cells in medicine range from their inclusion in disease modeling and drug discovery to cell transplantation and regenerative therapies. However, before this promise can be realized several obstacles must be overcome, including the control of stem cell differentiation, allogeneic rejection and limited cell availability. This will require an improved understanding of the mechanisms that govern stem cell potential and the development of robust methods to efficiently control their fate. Recently, a number of small molecules have been identified that can be used both in vitro and in vivo as tools to expand stem cells, direct their differentiation, or reprogram somatic cells to a more naive state. These molecules have provided a wealth of insights into the signaling and epigenetic mechanisms that regulate stem cell biology, and are already beginning to contribute to the development of effective treatments for tissue repair and regeneration.     

Synthesis and evaluation of new phosphonic acid‐functionalized acrylamides with potential biomedical applications

Phosphorus‐containing acidic monomers are able to interact with the inorganic phase of mineralized tissues such as enamel, dentin, and bone. From this perspective, three phosphonic acid‐containing acrylamide monomers with different lengths of alkyl chains were synthesized to be used for both self‐etching dental adhesives and mineralized hydrogel scaffolds. Monomers were synthesized by the reaction of α‐aminophosphonates (diethyl aminomethylphosphonate, diethyl 2‐aminobutan‐2‐ylphosphonate, and diethyl 2‐aminooctan‐2‐ylphosphonate) with acryloyl chloride followed by the hydrolysis of phosphonate groups by using trimethylsilyl bromide. The properties such as pH in the range of mild self‐etching adhesives, hydrolytic stability, high rate of copolymerizations with 2‐hydroxyethyl methacrylate (HEMA) and HEMA/glycerol dimethacrylate, giving high‐molecular‐weight polymers on thermal polymerization, and strong decalcification ability of hydroxyapatite make these monomers good candidates for self‐etching adhesives, although no appreciable effect of the number and size of the α‐substituents was observed. Hydrogel scaffolds containing phosphonic acid groups were fabricated, characterized, and mineralized. Altogether, the results suggest that these phosphonic acid‐containing monomers have suitable properties to be used in fabrication of biomaterials for both dental and bone tissue engineering applications. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 2755–2767     

Novel hepatoma‐targeting micelles based on chemoenzymatic synthesis and self‐assembly of galactose‐functionalized ribavirin‐containing amphiphilic random copolymer

Hepatoma‐targeting micelles were successfully prepared by self‐assembly of galactose‐functionalized ribavirin‐containing amphiphilic random copolymer as novel drug delivery vehicles. The ribavirin‐containing random copolymer with galactose as the targeting ligand was facilely synthesized by combining enzymatic transesterification with radical polymerization and fully characterized by FTIR, NMR, and GPC. The formation of micelle‐type aggregates from the random copolymer was verified by UV–vis and fluorescence spectroscopy using pyrene as the guest molecule. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) experiments revealed that the micelles were well dispersed as spherical nanoparticles in water, whose hydrodynamic diameter was 217 ± 19 nm. Their biological recognition to fluorescein‐labeled peanut agglutinin investigated by confocal laser scanning microscopy (CLSM) proved the existence of hydrophilic galactose targeting moieties on the surface of micelles. Cell cytotoxicity tests and the inhibition experiment of galactose performed by MTT assay showed that the micelles had evident targeting function to hepG2 cells and the galactose moieties on the surface of micelles mediated cellar uptake of micelles. In vitro release studies indicated that ribavirin could be slowly released from the copolymer with pseudo zero‐order kinetics. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 2734–2744, 2008     

Fabrication and characterization of composites composed of a bioresorbable polyester matrix and surface modified calcium carbonate whisker for bone regeneration

This work aims to evaluate the potential of a bioresorbable composite as material for bone regeneration. Surface‐modified calcium carbonate whiskers (CCWs) were prepared by grafting of ethylene glycol (EG) using 1,6‐hexamethylene diisocyanate as coupling agent, followed by ring‐opening polymerization of l ‐lactide initiated by the hydroxyl group of EG. The resulting PLLA‐EG‐g‐CCW was used as filler to reinforce a bioresorbable terpolymer, poly(l ‐lactide‐co‐trimethylene carbonate‐co‐glycolide) (PLTG). The mechanical properties and thermal stability of the PLTG/PLLA‐EG‐g‐CCW composites were greatly improved. Compared with neat PLTG, a 39.3% increase in tensile strength and 26.7% increase in elongation at break were obtained for the composite with 2 wt% PLLA‐EG‐g‐CCW filler. This was assigned to the reinforcement effect of evenly dispersed PLLA‐EG‐g‐CCW in the polymeric matrix. In fact, entanglement of PLLA grafts at the surface of PLLA‐EG‐g‐CCW with PLTG chains results in a homogeneous distribution of the filler in the matrix. Thus, the composites are simultaneously strengthened and toughened. The cytocompatibility of the materials was evaluated from cell morphology and 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay using L929 mouse fibroblast cell line. The results indicate that the composite presents very low cytotoxicity. Copyright © 2017 John Wiley & Sons, Ltd.     

Construction of peptide-vehicles,bioconjugates having modules for cancer cell surface capture and cell-penetrating peptide with anticancer agents

Recently molecular targeting therapy has been applied to cancer chemotherapy, although in some cases side-effects are not negligible. Based on our bio-detection concept, that is, protein–protein interaction can be mimicked by using peptides, a novel cell-targeting concept designated peptide-vehicle has been proposed, which has conjugates consisting of the cancer cell recognition and cell penetrating peptides with anticancer drugs. The cancer cell surface protein can be captured by a cyclotide, containing protease resistant d-cystine. A library of cell penetrating peptides has been prepared and conjugated to the cyclotide. Anticancer molecules were recovered after clinical use, which were pooled, purified, and derivatized for loading into the vehicle. The present Letter describes construction of peptide-vehicles, bioconjugates focusing on more efficiency and cancer cell selective delivery for anticancer drugs.