Flexible biomimetic block copolymer composite for temperature and long-wave infrared sensing.

Biological compounds often provide clues to advance material designs. Replicating their molecular structure and functional motifs in artificial materials offers a blueprint for unprecedented functionalities. Here, we report a flexible biomimetic thermal sensing (BTS) polymer that is designed to emulate the ion transport dynamics of a plant cell wall component, pectin. Using a simple yet versatile synthetic procedure, we engineer the physicochemical properties of the polymer by inserting elastic fragments in a block copolymer architecture, making it flexible and stretchable. The thermal response of our flexible polymer outperforms current state-of-the-art temperature sensing materials, including vanadium oxide, by up to two orders of magnitude. Thermal sensors fabricated from these composites exhibit a sensitivity that exceeds 10 mK and operate stably between 15° and 55°C, even under repeated mechanical deformations. We demonstrate the use of our flexible BTS polymer in two-dimensional arrays for spatiotemporal temperature mapping and broadband infrared photodetection.

Chemical characterization of constituents from Polygonatum cyrtonema Hua and their cytotoxic and antioxidant evaluation.

Twenty-four compounds were isolated from the roots of Polygonatum cyrtonema Hua, including a new octopamine dimer, named trans-bis(N-feruloyl)octopamine (1). The structure was established on the basis of spectroscopic and chemical methods. All the extracts and compounds were evaluated for cytotoxic and antioxidant activities by using MTT and chemiluminescence assay. The extracts showed activity against MCF-7 and HepG-2 cell lines from IC50 0.30 to 1.01 mg mL-1. Compound 3 exhibited activity against HepG-2 cell lines with IC50 8.99 µM. Compound 7 exhibited activity against Hela cell lines with IC50 2.53 µM and BGC-823 cell lines with IC50 7.77 µM. Moreover, compound 7 showed antioxidant with IC50 12 µM compared to the positive control with IC50 77 µM. Compound 16 exhibited activity against HepG-2 cell lines with IC50 1.05 µM and MCF-7 cell lines with IC50 1.89 µM. These results indicated that this plant might be potential in natural medicine and healthy food.

Triplex Hybridization of siRNA with Bifacial Glycopolymer Nucleic Acid Enables Hepatocyte-Targeted Silencing.

Herein, we describe a versatile non-covalent strategy for packaging nucleic acid cargo with targeting modalities, based on triplex hybridization of oligo-uridylate RNA with bifacial polymer nucleic acid (bPoNA). Polyacrylate bPoNA was prepared and side chain-functionalized with N-acetylgalactosamine (GalNAc), which is known to enable delivery to hepatocytes and liver via binding to the asialoglycoprotein receptor (ASGPR). Polymer binding resulted in successful delivery of both native and synthetically modified siRNAs to HepG2 cells in culture, yielding in low nanomolar IC50 silencing of the endogenous ApoB target, in line with observations of expected Dicer processing of the polymer-siRNA targeting complex. Indeed, in vitro Dicer treatment of the polymer complex indicated that triplex hybridization does not impede RNA processing and release from the polymer. The complex itself elicited a quiescent immunostimulation profile relative to free RNA in a cytokine screen, setting the stage for a preliminary in vivo study in a high-calorie-diet mouse model. Gratifyingly, we observed significant ApoB silencing in a preliminary animal study, validating bPoNA as an in vivo carrier platform for systemic siRNA delivery. Thus, this new siRNA carrier platform exhibits generally useful function and is accessible through scalable synthesis. In addition to its utility as a carrier, the triplex-hybridizing synthetic platform could be useful for optimization screens of siRNA sequences using the identical polymer carriers, thus alleviating the need for covalent ligand modification of each RNA substrate.

High-Capacity Drug Carriers from Common Polymer Amphiphiles.

We report herein a dual-purpose role for polyacidic domains in an aqueous-phase polymer amphiphile assembly. In addition to their typical role as ionized water-solubilizing and self-repulsive motifs, we find that polycarboxylic acid domains uniquely enable high levels of hydrophobic drug encapsulation. By attenuated total reflectance infrared spectroscopy, we find significant differences in the carbonyl stretching region of the nanoparticles formed by polyacidic amphiphiles relative to those in soluble, single-domain poly(acrylic acid), suggesting that stabilization may be derived from limited ionization of the carboxylate groups upon assembly. Acidic-hydrophobic diblock polyacrylates were prepared and coassembled with up to 60 wt % camptothecin (CPT) into nanoparticles, the highest loading reported to date. Controlled release of bioactive CPT from polymer nanoparticles is observed, as well as protection from human serum albumin-induced hydrolysis. Surface protection with PEG limits uptake of the CPT-loaded nanoparticles by MCF-7 breast cancer cells, as expected. Acidic-hydrophobic polymer amphiphiles thus have the hallmarks of a useful and general drug delivery platform and are readily accessible from living radical polymerization of cheap, commercially available monomers. We highlight here the potential utility of this common polymer design in high-capacity, controlled-release polymer nanoparticle systems.

Synthetic Polymer Hybridization with DNA and RNA Directs Nanoparticle Loading, Silencing Delivery, and Aptamer Function.

We report herein discrete triplex hybridization of DNA and RNA with polyacrylates. Length-monodisperse triazine-derivatized polymers were prepared on gram-scale by reversible addition-fragmentation chain-transfer polymerization. Despite stereoregio backbone heterogeneity, the triazine polymers bind T/U-rich DNA or RNA with nanomolar affinity upon mixing in a 1:1 ratio, as judged by thermal melts, circular dichroism, gel-shift assays, and fluorescence quenching. We call these polyacrylates "bifacial polymer nucleic acids" (bPoNAs). Nucleic acid hybridization with bPoNA enables DNA loading onto polymer nanoparticles, siRNA silencing delivery, and can further serve as an allosteric trigger of RNA aptamer function. Thus, bPoNAs can serve as tools for both non-covalent bioconjugation and structure-function nucleation. It is anticipated that bPoNAs will have utility in both bio- and nanotechnology.

Small-molecule/polymer recognition triggers aqueous-phase assembly and encapsulation.

An aqueous-soluble melamine polymer was condensed into nanoparticles by specific heterocycle binding interactions with 5-fluorouracil (5-FU) or cyanuric acid (CA). Small-molecule/polymer recognition of this type exhibits a clear exothermic binding signature and is sufficiently robust to induce macromolecular assembly in water. Polymer amphiphiles with melamine sites in the hydrophobic block could be stably loaded with up to 17% weight 5-FU. Macromolecular assembly with 5-FU or CA requires specific hydrogen-bonding recognition between 5-FU/CA and polymer-displayed melamine; assembly may be blocked by melamine methylation. Melamine and 5-fluorouracil complexes were analyzed by X-ray crystal structure determination, which revealed the expected 5-FU/melamine hydrogen-bonding interactions.