Cationic (Co)polymers Based on N-Substituted Polyacrylamides as Carriers of Bio-macromolecules: Polyplexes, Micelleplexes, and Spherical Nucleic Acidlike Structures.

Novel N-substituted polyacrylamides bearing a cycle with two tertiary amines, poly(4-methyl-piperazin-1-yl)-propenone (PMPP) and its block copolymers with polylactide (PMPP-b-PLA), are synthesized and characterized. The homopolymers are water-soluble, whereas the block copolymers self-assemble in aqueous solution into a small size (Rh around 30 nm), are narrowly distributed, and exhibit core-shell micelles with good colloidal stability. Both the homopolymers and copolymer micelles are positively charged (ζ-potentials in the 13.8-17.6 mV range), which are employed for formation of electrostatic complexes with oppositely charged DNA. Complexes (polyplexes, micelleplexes, and spherical nucleic acidlike structures) in a wide range of N/P (amino to phosphate groups) ratios are prepared with short (115 bp) and long (2000 bp) DNA. The behavior and physicochemical properties of the resulting nanocarriers of DNA are strongly dependent on the polymer/polymer micelles' characteristics and the DNA chain length. All systems exhibit low cytotoxicity and good cellular uptake ability and show promise for gene delivery and regulation.

Functionalization of polyacrylamide for nanotrapping positively charged biomolecules.

Engineering new materials which are capable of trapping biomolecules in nanoscale quantities, is crucial in order to achieve earlier diagnostics in different diseases. This article demonstrates that using free radical copolymerization, polyacrylamide can be successfully functionalized with specific synthons for nanotrapping positively charged molecules, such as numerous proteins, through electrostatic interactions due to their negative charge. Specifically, two functional random copolymers, acrylamide/acrylic acid (1) and acrylamide/acrylic acid/N-(pyridin-4-yl-methyl)acrylamide (2), whose negative net charges differ in their water solutions, were synthetized and their ability to trap positively charged proteins was studied using myoglobin as a proof-of-concept example. In aqueous solutions, copolymer 1, whose net charge for a 100 chain fragment (Q pH 6/M) is -1.323 × 10-3, interacted with myoglobin forming a stable monodisperse nanosuspension. In contrast, copolymer 2, whose value of Q pH 6/M equals -0.361 × 10-3, was not able to form stable particles with myoglobin. Nevertheless, thin films of both copolymers were grown using a dewetting process, which exhibited nanoscale cavities capable of trapping different amounts of myoglobin, as demonstrated by bimodal AFM imaging. The simple procedures used to build protein traps make this engineering approach promising for the development of new materials for biomedical applications where trapping biomolecules is required.