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Protein nanoparticles are a promising approach for nanotherapeutics, as proteins combine versatile chemical and biological function with controlled biodegradability. In this work, the development of an adaptable synthesis method is presented for synthetic protein nanoparticles (SPNPs) based on reactive electrojetting. In contrast to past work with electrohydrodynamic cojetting using inert polymers, the jetting solutions are comprised of proteins and chemically activated macromers, designed to react with each other during the processing step, to form insoluble nanogel particles. SPNPs made from a variety of different proteins, such as transferrin, insulin, or hemoglobin, are stable and uniform under physiological conditions and maintain monodisperse sizes of around 200 nm. SPNPs comprised of transferrin and a disulfide containing macromer are stimuli-responsive, and serve as markers of oxidative stress within HeLa cells. Beyond isotropic SPNPs, bicompartmental nanoparticles containing human serum albumin and transferrin in two distinct hemispheres are prepared via reactive electrojetting. This novel platform provides access to a novel class of versatile protein particles with nanoscale architectures that i) can be made from a variety of proteins and macromers, ii) have tunable biological responses, and iii) can be multicompartmental, a prerequisite for controlled release of multiple drugs., (© 2020 Wiley-VCH GmbH.)

Nanomaterials have great potential to offer effective treatment against devastating diseases by providing sustained release of high concentrations of therapeutic agents locally, especially when the route of administration allows for direct access to the diseased tissues. Biodegradable polyphosphoester-based polymeric micelles and shell cross-linked knedel-like nanoparticles (SCKs) have been designed from amphiphilic block-graft terpolymers, PEBP-b-PBYP-g-PEG, which effectively incorporate high concentrations of paclitaxel (PTX). Well-dispersed nanoparticles physically loaded with PTX were prepared, exhibiting desirable physiochemical characteristics. Encapsulation of 10 wt% PTX, into either micelles or SCKs, allowed for aqueous suspension of PTX at concentrations up to 4.8 mg/mL, as compared to <2.0 μg/mL for the aqueous solubility of the drug alone. Drug release studies indicated that PTX released from these nanostructures was defined through a structure-function relationship, whereby the half-life of sustained PTX release was doubled through cross-linking of the micellar structure to form SCKs. In vitro, physically loaded micellar and SCK nanotherapeutics demonstrated IC50 values against osteosarcoma cell lines, known to metastasize to the lungs (CCH-OS-O and SJSA), similar to the pharmaceutical Taxol formulation. Evaluation of these materials in vivo has provided an understanding of the effects of nanoparticle structure-function relationships on intratracheal delivery and related biodistribution and pharmacokinetics. Overall, we have demonstrated the potential of these novel nanotherapeutics toward future sustained release treatments via administration directly to the sites of lung metastases of osteosarcoma.

Nanocomposite polymers are prepared using a new sustainable materials synthesis process in which d-Limonene functions simultaneously both as a solvent for recycling polystyrene (PS) waste and as a monomer that undergoes UV-catalyzed thiol-ene polymerization reactions with polythiol comonomers to afford polymeric products composed of precipitated PS phases dispersed throughout elastomeric poly(thioether) networks. These blended networks exhibit mechanical properties that greatly exceed those of either polystyrene or the poly(thioether) network homopolymers alone., (© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The successful development of degradable polymeric nanostructures as optical probes for use in nanotheranostic applications requires the intelligent design of materials such that their surface response, degradation, drug delivery, and imaging properties are all optimized. In the case of imaging, optimization must result in materials that allow differentiation between unbound optical contrast agents and labeled polymeric materials as they undergo degradation. In this study, we have shown that use of traditional electrophoretic gel-plate assays for the determination of the purity of dye-conjugated degradable nanoparticles is limited by polymer degradation characteristics. To overcome these limitations, we have outlined a holistic approach to evaluating dye and peptide-polymer nanoparticle conjugation by utilizing steady-state fluorescence, anisotropy, and emission and anisotropy lifetime decay profiles, through which nanoparticle-dye binding can be assessed independently of perturbations, such as those presented during the execution of electrolyte gel-based assays. This approach has been demonstrated to provide an overall understanding of the spectral signature-structure-function relationship, ascertaining key information on interactions between the fluorophore, polymer, and solvent components that have a direct and measurable impact on the emissive properties of the optical probe. The use of these powerful techniques provides feedback that can be utilized to improve nanotheranostics by evaluating dye emissivity in degradable nanotheranostic systems, which has become increasingly important as modern platforms transition to architectures intentionally reliant on degradation and built-in environmental responses.

Copper catalyzed azide-alkyne cycloaddition (CuAAC) was employed to synthesize DNA block copolymers (DBCs) with a range of polymer blocks including temperature-responsive poly(N-isoproylacrylamide) (poly(NIPAM)) and highly hydrophobic poly(styrene). Exceptionally high yields were achieved at low DNA concentrations, in organic solvents, and in the absence of any solid support. The DNA segment of the DBC remained capable of sequence-specific hybridization: it was used to assemble a precisely defined nanostructure, a DNA tetrahedron, with pendant poly(NIPAM) segments. In the presence of an excess of poly(NIPAM) homopolymer, the tetrahedron-poly(NIPAM) conjugate nucleated the formation of large, well-defined nanoparticles at 40 °C, a temperature at which the homopolymer precipitated from solution. These composite nanoparticles were observed by dynamic light scattering and cryoTEM, and their hybrid nature was confirmed by AFM imaging. As a result of the large effective surface area of the tetrahedron, only very low concentrations of the conjugate were required in order for this surfactant-like behavior to be observed.

The synthesis and photophysical characterization of a chromophore-bridged block copolymer system is presented. This system is based on a dithiomaleimide (DTM) functional group as a highly emissive functionality which can readily be incorporated into polymeric scaffolds. A key advantage of this new reporter group is its versatile chemistry, ease of further functionalization, and notably small size, which allows for ready incorporation without affecting or disrupting the self-assembly process critical to the formation of core-shell polymeric contrast and drug delivery agents. We demonstrate the potential of this functionality with a diblock system which has been shown to be appropriate for micellization and, when in the micellar state, does not self-quench. The block copolymer is shown to be significantly more emissive than the lone dye, with a concentration-independent emission and anisotropy profile from 1.5 mM to 0.15 μM. An emission lifetime and anisotropy decay comparison of the block copolymer to its micelle displays that time-domain fluorescence lifetime imaging (FLIM) is able to rapidly resolve differences in the supramolecular state of this block-dye-block polymer system. Furthermore, the ability to resolve these differences in the supramolecular state means that the DTM micelles are capable of self-reporting when disassembly occurs, simply by monitoring with FLIM. We demonstrate the great potential for in vitro applications that this system provides by using FLIM to observe micelle disassembly in different vascular components of rat hippocampal tissue. In total this system represents a new class of in-chain emitter which is appropriate for application in quantitative imaging and the tracking of particle degradation/disassembly events in biological environments.

Dithiomaleimides (DTMs) with alkyl substituents are shown to be a novel class of highly emissive fluorophores. Variable solubility and further functionalization can easily be tailored through the choice of N and S substituents. Inclusion of a DTM unit into a ROP/RAFT initiator or insertion into the disulfide bond of salmon calcitonin (sCT) demonstrates the utility for fluorescent labeling of polymers and proteins. Simultaneous PEGylation and fluorescent labeling of sCT is also demonstrated, using the DTM unit as both a linker and a fluorophore. It is anticipated that DTMs will offer an attractive alternative to commonly used bulky, planar fluorophores.

The reported diblock brush terpolymer displays the fundamental advantages of high macromolecular and regiochemical control in simultaneous top ‐ down/bottom ‐ up construction of advanced positive ‐ tone photoresist materials. By selective partition the substrate adhesion, surface ‐ active migration, and chemically ‐ reactive deblocking functional compositions into the cylindrical polymer brush architectures, large ‐ areas of vertical alignment of the polymers within thin films are realized. The bottom ‐ up premeditated system enables effective top ‐ down lithography to produce near ‐ molecular pixel resolution (2–3 molecules) at low operation dosage. [ABSTRACT FROM AUTHOR]

The article focuses on the synthesis of tin oxide (SnO2) nanoparticles stabilized by dendritic polymers. Two fourth-generation dendritic architectures: poly(propyleneimine) and poly(amidoamine) with diaminobutyl cores were employed for the synthesis. An aqueous or ethanolic solution containing sodium stannate and a polymeric host was first stirred for about 2 hours to ensure saturated host-guest chelation. Gaseous carbon dioxide was then bubbled through the room-temperature mixture with vigorous stirring which afforded a light yellow solution. On more addition of stannate a white cloudy precipitate formed upon reaction with carbon dioxide due to the presence of free SnO32- ions solution which was confirmed by elemental analysis, and powder XRD.

A novelpolyphosphoester (PPE) with vinyl ether side chain functionalitywas developed as a versatile template for postpolymerization modifications,and its degradability and biocompatibility were evaluated. An organocatalyzedring-opening polymerization of ethylene glycol vinyl ether-pendantcyclic phosphotriester monomer allowed for construction of poly(ethyleneglycol vinyl ether phosphotriester) (PEVEP). This vinyl ether-functionalizedPPE scaffold was coupled with hydroxyl- or thiol-containing modelsmall molecules via three different types of conjugation chemistriesthiol–ene“click” reaction, acetalization, or thio-acetalizationreactionto afford modified polymers that accommodated eitherstable thio–ether or hydrolytically labile acetal or thio–acetallinkages. Amphiphilic diblock copolymers of poly(ethylene glycol)and PEVEP formed well-defined micelles with a narrow and monomodalsize distribution in water, as confirmed by dynamic light scattering(DLS), transmission electron microscopy, and atomic force microscopy.The stability of the micelles and the hydrolytic degradability ofthe backbone and side chains of the PEVEP block segment were assessedby DLS and nuclear magnetic resonance spectroscopy (1Hand 31P), respectively, in aqueous buffer solutions atpH values of 5.0 and 7.4 and at temperatures of 25 and 37 °C.The hydrolytic degradation products of the PEVEP segments of the blockcopolymers were then identified by electrospray ionization, gas chromatography,and matrix-assisted laser desorption/ionization mass spectrometry.The parent micelles and their degradation products were found to benon-cytotoxic at concentrations up to 3 mg/mL, when evaluated withRAW 264.7 mouse macrophages and OVCAR-3 human ovarian adenocarcinomacells. [ABSTRACT FROM AUTHOR]