Tetraphenylethylene-based gemini surfactant as nonviral gene delivery system: DNA complexation, gene transfection and cellular tracking

Abstract Gemini surfactant (GS) has been proved to be a powerful system for nonviral gene delivery. Herein, a family of tetraphenylethylene (TPE)-based GS possessing different lengths of hydrophobic tails and different linkages between the TPE and [12]aneN 3 moieties ( 1a , 2a , 1b and 2b ) were synthesized for facilitating DNA condensation, promoting gene transfection and tracing cellular fate of GS/DNA complex. These GS can readily self-assemble into micelles in aqueous solution with ultralow critical micelle concentrations (CMC, 1.2−1.3 μM), and have good pH-/photo-stabilities and strong DNA binding capacities. DNA nanoparticles condensed by the above GSs are in a range of 90−110 nm and in the form of spherical morphology showing great stability in the absence and presence of fetal bovine serum. Biological activities including cytotoxicity, cell transfection and cellular internalization were systematically investigated. Results revealed that good biocompatibility ( e.g. , all the tested cells showed more than 80% of cell viabilities at 30 μM) and high transfection efficiency ( e.g. , 2a /DOPE showed 4.5-fold TE of Lipo2000 in HeLa cell line) were conferred to these GSs. Moreover, the spatiotemporal messages regarding the cellular uptake, location and release of the DNA condensates were clearly captured by the fluorescence changes. Particularly, the impacts of the hydrophobic length and linkage on the physicochemical properties and biological activities were discussed in detail, shedding light on the corresponding structure-activity relationship. The results have demonstrated that TPE-based GSs are very promising as new gene delivery carrier and instructive for rational expansion of novel nonviral gene system.