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

Affiliation

Haladjova E(1), Dimitrov I(1), Davydova N(2), Todorova J(3), Ugrinova I(3), Forys A(4), Trzebicka B(4), Rangelov S(1).
Author information:
(1)Institute of Polymers, Bulgarian Academy of Sciences, Sofia 1113, Bulgaria.
(2)A.N. Nesmeyanov Institute of Organoelement Compounds of Russian Academy of Sciences, Moscow 119991, Russia.
(3)Institute of Molecular Biology, Bulgarian Academy of Sciences, Sofia 1113, Bulgaria.
(4)Centre of Polymer and Carbon Materials, Polish Academy of Sciences, Marie Curie-Sklodowskiej 34, Zabrze 41-819, Poland.

Abstract

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.