Structure of micelleplexes formed between QPDMAEMA-b-PLMA amphiphilic cationic copolymer micelles and DNA of different lengths. (5th March 2022)

• Record Type: Journal Article
• Authors: Chrysostomou, Varvara; Forys, Aleksander; Trzebicka, Barbara; Demetzos, Costas; Pispas, Stergios
• Is Part Of: European polymer journal. Volume 166(2022)
• Publication Date: 2022-03-05
• Subjects: Non-viral vectors -- Gene delivery -- Micelleplexes -- Cationic polyelectrolytes -- Block copolymers -- Nucleic acids; Polymers -- Periodicals; Polymerization -- Periodicals; Polymères -- Périodiques; Polymérisation -- Périodiques; Polymerization; Polymers; Periodicals; Electronic journals; 547.705
• DOI: 10.1016/j.eurpolymj.2022.111048
• Languages: English
• ISSNs: 0014-3057

Abstract

Graphical abstract: Highlights: QPDMAEMA-b-PLMA copolymer micelles were found to complex with linear DNA of different lengths. Fluorescence spectroscopy confirmed complexation of QPDMAEMA-b-PLMA micelles with DNAs. DLS revealed the formation of stable nanosized micelleplexes, at different N/P ratios. The formation of spherical and worm-like micelleplexes was visualized by Cryo-TEM. The morphology of micelleplexes depends on micelle characteristics and DNA length. Abstract: We study the structures of micelleplexes formed by quaternized poly(2-(dimethylamino) ethyl methacrylate)-b-poly(lauryl methacrylate) (QPDMAEMA-b-PLMA) amphiphilic cationic copolymer micelles interacting electrostatically with linear DNA of different lengths (113 and 2000 base pairs). QPDMAEMA-b-PLMA copolymers form micelles in aqueous milieu, with PLMA hydrophobic cores and QPDMAEMA cationic coronas. Nanosized micelleplexes were formed after mixing QPDMAEMA-b-PLMA micelles with DNAs, in a wide range of N/P ratios (nitrogen (N) of amine group of QPDMAEMA over phosphate (P) groups of DNA), as shown by Ultraviolet–Visible (UV–Vis) and fluorescence spectroscopy. Light scattering techniques demonstrated the formation of well-defined micelleplexes with monomodal and narrow size distributions, whose size and surface charge vary according to the N/P ratio. Micelleplexes presented stability under certain salt concentration. Spherical and worm-like micelleplexes were visualized by cryogenic transmission electron microscopy (Cryo-TEM). Overall, QPMDAEMA-b-PLMA micelles can efficiently interact with DNA. The stability, morphology and complexation of the micelleplexes were found to depend on copolymer molecular mass, the hydrophilic/hydrophobic ratio, the micellar structure, the length of DNA, the N/P ratio and the ionic strength. The findings demonstrate that QPDMAEMA-b-PLMA polyelectrolyte copolymer micelles have prospects for their application as non-viral vectors for nucleic acids delivery and gene therapy.