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

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

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

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” (bP_oNAs). Nucleic acid hybridization with bP_oNA enables DNA loading onto polymer nanoparticles, siRNA silencing delivery, and can further serve as an allosteric trigger of RNA aptamer function. Thus, bP_oNAs can serve as tools for both non-covalent bioconjugation and structure–function nucleation. It is anticipated that bP_oNAs will have utility in both bio- and nanotechnology

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