Amphiphilic Copolymer-Lipid Chimeric Nanosystems as DNA Vectors

Abstract

Lipid-polymer chimeric (hybrid) nanosystems are promising platforms for the design of effective gene delivery vectors. In this regard, we developed DNA nanocarriers comprised of a novel poly[(stearyl methacrylate-co-oligo(ethylene glycol) methyl ether methacrylate] [P(SMA-co-OEGMA)] amphiphilic random copolymer, the cationic 1,2-dioleoyl-3-(trimethylammonium) propane (DOTAP), and the zwitterionic L-α-phosphatidylcholine, hydrogenated soybean (soy) (HSPC) lipids. Chimeric HSPC:DOTAP:P[(SMA-co-OEGMA)] nanosystems, and pure lipid nanosystems as reference, were prepared in several molar ratios of the components. The colloidal dispersions obtained presented well-defined physicochemical characteristics and were further utilized for the formation of lipoplexes with a model DNA of linear topology containing 113 base pairs. Nanosized complexes were formed through the electrostatic interaction of the cationic lipid and phosphate groups of DNA, as observed by dynamic, static, and electrophoretic light scattering techniques. Ultraviolet–visible (UV–Vis) and fluorescence spectroscopy disclosed the strong binding affinity of the chimeric and also the pure lipid nanosystems to DNA. Colloidally stable chimeric/lipid complexes were formed, whose physicochemical characteristics depend on the N/P ratio and on the molar ratio of the building components. Cryogenic transmission electron microscopy (Cryo-TEM) revealed the formation of nanosystems with vesicular morphology. The results suggest the successful fabrication of these novel chimeric nanosystems with well-defined physicochemical characteristics, which can form stable lipoplexes.

Keywords

• non-viral vectors
• gene delivery
• cationic lipids
• amphiphilic random copolymers
• chimeric/hybrid lipoplexes