Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used over-the-counter drugs and their uncontrolled disposal is a significant environmental concern. Although their fluorescent sensing is a desirable method of detection for its sensitivity and simplicity, the structural similarity of the drugs makes the design of selective sensors highly challenging. A thiourea-based fluorescent functional monomer was identified in this work to enable highly efficient synthesis of molecularly imprinted nanoparticle (MINP) sensors for NSAIDs such as Indomethacin or Tolmetin. Micromolar binding affinities were obtained in aqueous solution, with binding selectivities comparable to those reported for polyclonal antibodies. The detection limit was ~50 ng/mL in aqueous solution, and common carboxylic acids such as acetic acid, benzoic acid, and citric acid showed negligible interference.

A series of functional nanogels were synthesized by a step-growth mechanism that involved diisocyanate addition to a modest stoichiometric excess of multi-thiols. Nanogels with sizes less than 10 nm were obtained as room temperature liquids with residual thiol groups used to attach methacrylate functionality. Depending on nanogel structure, bulk nanogel properties varied widely, as did the properties of the nanogel-derived and nanogel-modified polymers. Photopolymerization of the reactive nanogels in combination with a dimethacrylate monomer showed dramatically enhanced reaction rate and conversion compared with the dimethacrylate homopolymer. Polymerization shrinkage/ stress as well as mechanical properties of the polymer networks were controlled by changing the ratio of nanogels and dimethacrylate monomers used in formulations. Thus, this study shows the potential of step-growth nanogels for beneficial changes in resin reactivity and application-based performance.

Here we present hyaluronic acid (HA) hydrogels crosslinked via thiol-ene reaction initiated by visible blue light exposure in the presence of riboflavin phosphate (RFP). The gelation procedure is rapid and proceeds as effectively with exposure to blue light as it does with UV light. We successfully initiated the thiol-ene reaction by RFP with blue light, which triggered gelation that proceeds over about 5 min at 36 °C after an initial small change in modulus upon light exposure. Gel transparency was also evaluated, and the HA gel exhibited over 80% transmittance in the visible spectrum. The degradation and protein release kinetics of the photo-crosslinked HA hydrogel are also presented. The capacity of blue light to initiate thiol-ene reaction was equal to or more effective than UV light of the same energy. The cytocompatibility of hydrogels was evaluated using corneal fibroblasts, and the light-induced fabrication procedure and resultant gel materials did not affect cell viability. The results indicate that an RFP-based, BL-initiated photo-reaction to gelate HA may be an effective and promising modality for applications where gelation is desired.

Simvastatin was polymerized into copolymers to better control drug loading and release for therapeutic delivery. When using the conventional stannous octoate catalyst in ring-opening polymerization (ROP), reaction temperatures ≥200 °C were required, which promoted uncontrollable and undesirable side reactions. Triazabicyclodecene (TBD), a highly reactive guanidine base organocatalyst, was used as an alternative to polymerize simvastatin. Polymerization was achieved at 150 °C using 5 kDa methyl-terminated poly(ethylene glycol) (mPEG) as the initiator. ROP reactions with 2 kDa or 550 Da mPEG initiators were also successful using TBD at 150 °C instead of stannous octoate, which required a higher reaction temperature. Biodegradability of the poly(simvastatin) copolymer in phosphate-buffered saline was also improved, losing twice as much mass than the copolymer synthesized via stannous octoate. The three copolymers exhibited modified rates of simvastatin release, demonstrating tunablity for drug delivery applications.

A functional anticoagulant and anti-bacterial coating for polyethylene (PE) films is described. The stepwise preparation of this nanocomposite surface coating involves O plasma etching of PE film, carbodiimide coupling of cysteamine to the etched PE film, binding of Ag to sulfhydryl groups of cysteamine, and assembly of heparin capped AgNPs on the PE film. The nanocomposite film and its components were characterized by H-nuclear magnetic resonance spectroscopy, attenuated total reflectance-Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and field emission-scanning electron microscopy. The resulting PE films demonstrate anticoagulant activity using a hemoglobin whole blood clotting assay, and anti-bacterial activity against 3551 (Gram-positive) and BL21 (Gram-negative) bacteria. The hydrophilicity of the heparin coated PE was determined by contact angle measurements; and the stability of the nanocomposite film, with respect to Ag leaching, was assessed by atomic absorption spectroscopy.

A new strategy for the synthesis of biodegradable high molecular weight N-(2-hydroxypropyl)methacrylamide (HPMA)-based polymeric carriers has been designed. An enzyme-sensitive, alkyne-functionalized, chain transfer agent (CTA-GFLG-alkyne; N(α)-(4-pentynoyl)-N(δ)-(4-cyano-4-(phenylcarbonothioylthio)pentanoyl-glycylphenylalanylleucylglycyl)-lysine) was synthesized and used to mediate the reversible addition-fragmentation chain-transfer (RAFT) polymerization and copolymerization of HPMA. Post-polymerization modification with 4,4'-azobis(azidopropyl 4-cyanopentanoate)resulted in the formation of heterotelechelic HPMA copolymers containing terminal alkyne and azide groups. Chain extension via click reaction resulted in high molecular weight multiblock copolymers. Upon exposure to papain, these copolymers degraded into the initial blocks. Similar results were obtained for copolymers of HPMA with N-methacryloylglycylphenylalanylleucylglycyl thiazolidine-2-thione and N-methacryloylglycylphenylalanylleucylglycyl-gemcitabine. The new synthetic method presented permits the synthesis of biocompatible, biodegradable high molecular weight HPMA copolymer-anticancer drug conjugates that possess long-circulation times and augmented accumulation in solid tumor tissue due to the enhanced permeability and retention effect.

A key challenge in developing protein therapeutics or imaging agents that work against cytosolic targets is the intracellular delivery barrier. Here, we show that the pH-responsive, membrane-destabilizing polymer, poly (propylacrylic acid) (PPAA), can strongly enhance target cell killing through the intracellular delivery of a functional proapoptotic peptide. The Bak BH3 peptide induces apoptosis via antagonization of suppressor targets such as Bcl-2 and Bcl-x(L). A genetically-engineered streptavidin that contains an N-terminal TAT peptide sequence was used to optimize the pinocytotic cell uptake of biotinylated BH3 peptide and end-biotinylated PPAA. Fluorescence microscopic analysis of DAPI-stained HELA cells was used to quantitate apoptosis. Approximately 30% of cells treated with TAT-SA:BH3 complexes revealed morphologically distinct nuclear condensation, a hallmark of apoptosis. The incorporation of biotinylated PPAA had the effect of markedly enhancing the killing effect of BH3 peptides by an additional 55% (p<0.001) to a total cell killing efficiency of 85%. Caspase-3 activity was up-regulated in a TAT-SA:BH3:PPAA dose-dependent manner. The induction of apoptosis with the TAT-SA:BH3:PPAA complex was abrogated with the L78A BH3 peptide, that had been previously shown to knock-out antagonization activity. The caspase and L78A peptide results demonstrate that the delivered BH3 is indeed working through the biologically relevant apoptosis signaling pathway. These studies establish the ability of PPAA to strongly enhance the intracellular delivery of a functional pro-apoptotic peptide. Together with the PPAA, the TAT-SA adaptor complex could prove useful as a carrier of peptide/protein cargo to cultured cells.

Novel surface-functionalized cross-linked nanogels were developed as a platform to allow conjugation of monoclonal antibodies (mAb) for targeted drug delivery. Well-defined diblock copolymers of poly(ethylene glycol)-b-poly(methacrylic acid) (PEG-b-PMA) with PEG terminal aldehyde functionality were synthesized by atom transfer radical polymerization (ATRP) and characterized by GPC and (1)H NMR. These copolymers were used to prepare nanogels via condensation of PEG-b-PMA with Ca(2+) ions into micelle-like aggregates, cross-linking of the PMA/Ca(2+) cores and removal of Ca(2+) ions. The resulting nanogels represent highly swollen spherical polyelectrolyte particles with free terminal aldehyde functionalities at the nonionic PEG chains. A reductive amination reaction between aldehyde groups and amino groups of mAb resulted in effective conjugation to the nanogels of mAb CC49 against tumor-associated glycoprotein 72 (TAG-72). The mAb retained the binding affinity to bovine submaxillary mucin after conjugation as shown by surface plasmon resonance (SPR). Therefore, aldehyde functionalized nanogels can be linked to mAb using a simple, one-step approach. They may have potential for targeted delivery of diagnostic and therapeutic agents to tumors.

Bioreducible polymers, which possess mainly disulfide linkages in the polymer structures, have appeared as ideal gene delivery carriers due to the high stability in extracellular physiological condition and bioreduction-triggered release of genetic materials, as well as decreased cytotoxicity because intracellular cytosol is a reducing environment containing high level of reducing molecules such as glutathione. This review will describe the initiation and recent advances in the development of bioreducible polymers for gene delivery, which includes reducibly cross-linked PEIs, polypeptides, polyion complex micelles, and poly(amido amine)s. There have been extensive researches performed to exhibit great gene delivery efficacy but still several important issues about pharmacokinetics or safety should be answered thoroughly for further rational design of bioreducible polymers having potentials in human gene delivery systems.

Polycationic systems based on poly(hexamethylene biguanide) (PHMBG), branched polyethyleneimine (PEI) and poly(N-vinylguanidine) (PVG) have been evaluated as heterogeneous catalysts for the transesterification of sunflower oil by methanol. Insoluble networks are synthesized via crosslinking of PHMBG by either 4,4'-methylenebis(N,N-diglycidylaniline) or polyisocyanate prepolymer, PEI with sebacoyl chloride, and PVG with 1,4-butanediol diglycidyl ether. PHMBG and its crosslinked networks appeared to be remarkably efficient catalysts, enabling 80-100% triglyceride conversion within 0.5 h at 70 degrees C. PEI-based networks catalyzed triglyceride transesterification with rates 8- to 12-fold slower than their PHMBG-based counterparts. The PVG-based networks, which were devoid of hydrophobic moieties, appeared to be inefficient catalysts due to limited accessibility of the basic guanidine groups to reactants. The PHMBG networks were shown to be recyclable by a simple centrifugal filtration. After 15 cycles of recovery and reuse, only 10-15% decline in performance was observed.

A new class of heterogeneous catalysts for asymmetric hydrogenation of enamides was synthesized using molecular imprinting technology. These new catalysts are molecularly imprinted polymers (MIPs) made from rhodium (I) and copper (II) complexes with the bis(oxazoline) chiral ligands. One of the Rh-MIPs showed 87% ee toward L-enantiomeric product while the Cu-MIP showed 82% ee toward D-enantiomeric product. Both MIPs are easy to separate and reusable.

Using m-aminophenylboronic acid (APBA) as a functional monomer, molecularly imprinted polymer (MIP) imprinted with bovine serum albumin (BSA) was fabricated on activated glass spheres under optimized conditions. Key factors in the prepolymerization reaction (between APBA and BSA), such as buffer pH, ionic strength and reaction time, were carefully optimized as previously reported [1]. The interaction between APBA and BSA during the prepolymerization stage was investigated and optimized, and ideal conditions for protein rebinding experiments were determined as well. Protein rebinding and enriching properties of polymers were studied in single and competitive binding protocols, respectively. The key point of the present paper is that the binding selectivity of polymers may be estimated by the amount of bound-protein recovered from a protein-saturated polymer. Results demonstrated that the selectivity of MIP towards its template protein is superior to that of non-imprinted polymer (NIP).