Understanding how the structures of surfactants in hybrid nanoparticles affect the compaction of ct-DNA for cellular uptake: presenting a highly efficient surfactant

Compaction of calf thymus DNA (ct-DNA) by two single-head-double-tailed surfactants with variable tail lengths <i>i.e.</i>, Dihexadecyldimethylammonium bromide (DDAB16) and Dioctadecyldimethylammonium bromide (DDAB18), and one triple-head-double-tailed surfactant <i>N</i>¹-dodecyl-<i>N</i>²-(2-(dodecyldimethylammonio)ethyl)-<i>N</i>¹,<i>N</i>¹,<i>N</i>²,<i>N</i>²-tetramethylethane-1,2-diaminium (MQAS12) has been studied. DDAB18 is found to be the most efficient, while MQAS12 is the least efficient for cellular uptake. Hybrid materials of surfactants and silica nanoparticles have better compaction efficiency due to the cooperative binding. Silica nanoparticles (∼100 nm)-DDAB18 hybrid materials can compact ct-DNA at a much lower concentration than a conventional surfactant, addressing the cytotoxicity issues. Hybrid materials formed with smaller silica nanoparticles (∼40 nm) have also been studied. The results obtained have been used to understand whether Coulombic and/or hydrophobic interactions are responsible for DNA compaction. The hydrophobicity per unit surface area (<i>P</i>) of hybrid nanoparticles has a significant role in DNA compaction. The <i>P</i> largely depends on the surfactants' structures and nanoparticles' sizes. Single-head-double-tailed surfactants with a comparatively smaller headgroup exhibit a large amount of adsorption on the nanoparticles' surfaces, producing a large <i>P</i>. DDAB18 appears to be a DNA intercalative binder. Fluorescence anisotropy decay data of 4,6-diamidino-2-phenylindole (DAPI) reveal the dynamics of ct-DNA at different stages of compaction. Cell viability of mouse mammary gland adenocarcinoma cells (4T1) and human embryonic kidney (HEK) 293 cell lines and <i>in vitro</i> cellular uptake of the gene to 4T1 cells have been investigated. This study provides ideas for designing efficient non-viral vectors. Overall, DDAB18-coated silica nanoparticles appear to be safe and effective DNA compaction agents that can carry nucleic acids for biomedical applications.