Controllable DNA Condensation by Mixed Cationic Gemini/Nonionic Surfactant Systems: Structure, Thermodynamics, and Cytotoxicity

Controllable DNA condensation is important for nucleic‐acid packaging and non‐viral gene‐delivery systems. This study aimed to determine how the composition of mixed nonionic C 12 E 10 and cationic gemini C 12 C 6 C 12 Br 2 surfactants regulates DNA condensation, structure, thermodynamics, and cytotoxicity. Calf thymus DNA was mixed with surfactant formulations containing different mole fractions of C 12 C 6 C 12 Br 2 . DNA–surfactant interactions were evaluated by UV spectroscopy, dynamic light scattering, ζ‐potential measurements, atomic force microscopy, differential scanning calorimetry, isothermal titration calorimetry (ITC), and cell‐viability assays. Increasing the gemini‐surfactant fraction induced a transition from extended DNA chains to compact globular complexes. Maximum condensation occurred at = 0.5, producing complexes of approximately 100 nm with positive ζ‐potentials. ITC showed that complex formation was spontaneous and predominantly entropy‐driven, consistent with counterion release, water reorganization, and hydrophobic association. At higher gemini fractions, overcharging and aggregate reorganization occurred. Incorporation of C 12 E 10 reduced cytotoxicity relative to the cationic C 12 C 6 C 12 Br 2 alone. These results demonstrate that mixed gemini/nonionic surfactant composition provides a controllable strategy for tuning DNA condensation and biocompatibility.