Cerasome as an Infusible, Cell-Friendly, and Serum-Compatible Transfection Agent in a Viral Size

Abstract

Alanine-based cationic lipid 1 having a (EtO)3SiCH2CH2CH2 group on the quaternized ammonium nitrogen forms a liposome which self-rigidifies via in situ sol-gel processes (Si-OEt + H2O --> Si-OH + EtOH followed by 2Si-OH --> Si-O-Si + H2O) on the surface. The resulting cerasome (partially ceramic- or silica-coated liposome) (60-70 nm) retains the integrity of such in the complexation with lucifarase-encoding plasmid DNA pGL3. The resultant pGL3 complex of infusible or monomeric cerasome in a viral size ( approximately 70 nm) exhibits a remarkable transfection performance toward HeLa and HepG2 cells with a 102-3-fold higher efficiency (relative to that of the nonsilylated reference lipid 2), minimized cytotoxicity, and serum compatibility. Reference lipid 2, i.e., alanine-based lipid having a simple quaternized ammonium headgroup, forms liposome (60-70 nm) which is less self-confined and more mobile undergoes DNA-induced fusion to give endocytosis-irrelevant and more toxic bigger (100-300 nm) particles. The silicon strategy thus provides a simple and widely applicable tool to overcome general problems associated with current technology of artificial gene delivery.

The intracellular plasmid DNA localization of cationic reducible cholesterol-disulfide lipids

“…To further examine the effect of serum [61,62], luciferase gene transfection efficacies with the CHOSS lipids as well as bPEI-25k as delivery vectors were investigated with the medium containing 10% FBS and the results are shown in Fig. 7b.…”

Chitosan enhanced gene delivery of cationic liposome via non-covalent conjugation

“…Gene therapy is expected to be an effective method to treat cancer, infection, innate immunodeficiency, and cardiovascular diseases (Verma and Somia 1997;Ewert et al 2006;Matsui et al 2006;Zhang et al 2007;Liu et al 2008;Zhang et al 2010). The development of reliable and efficient vectors delivering exogenous genes into target cells is urgently awaited which should be administered efficiently, safely, and repeatedly (Zhang et al 2007).…”

“…The development of reliable and efficient vectors delivering exogenous genes into target cells is urgently awaited which should be administered efficiently, safely, and repeatedly (Zhang et al 2007). In contrast to viral vectors, non-viral transfection agents, mainly including cationic lipids and cationic polymers, are believed to cause less safety problems due to their relative simplicity though non-specific cytotoxicity associated with cationic liposomes and polymers has been observed (Matsui et al 2006;Liu et al 2008), easy to manufacture in lager scale, and they can also deliver large pieces of DNA (Zhang et al 2010) and easy to modulate chemically for improvement of transfection efficiency.…”

Bionanocomposites Assembled by “From Bottom to Top” Method

“…Cerasomes were obtained from organoalkoxysilane pro-amphiphiles (1 and 2 in Fig. 7.26) under conditions of sol-gel reaction [335]. Diameter of nanoparticles is 70-300 nm and 20-100 nm for 1 and 2, respectively (see above Fig.…”