Arginine-tocopherol bioconjugated lipid vesicles for selective pTRAIL delivery and subsequent apoptosis induction in glioblastoma cells

Gemini Lipopeptide Bearing an Ultrashort Peptide for Enhanced Transfection Efficiency and Cancer-Cell-Specific Cytotoxicity

“…The dimeric cationic lipopeptide in the current study was synthesized using the bioconjugation strategy, as shown in Scheme 1. In tandem with our recent experience with arginine−tocopherol conjugates that have shown significant transfection and selectivity, 12 the current dimeric cationic lipid was hypothesized to be an effective mediator for selective gene therapy. The newly developed lipopeptide molecule contains multiple intracellularly labile bonds that may help in the release of genetic material intracellularly.…”

“…The reduction-responsive disulfide bond can be cleaved by intracellular reducing agents such as GSH, while the ester bonds can be broken by the enzymatic action of esterase to facilitate gene delivery . The role of the disulfide bridge in nanovesicles appears to be prominent as reported previously, where an increased release of siRNA by lipid nanovesicles with two lysine moieties bridged by a disulfide liker was observed. , The arginine–tocopherol conjugate (APT) was synthesized initially as reported previously, with the guanidine group still protected. The free amine on APT reacted with the two carboxylic acid groups of the cysteine molecule to make a peptide linker.…”

“…The arginine−tocopherol conjugate (APT) was synthesized initially as reported in our previous method. 12 Intermediate APT was then conjugated to (BOC-Cys-OH) 2 using the peptide chemistry approach. Intermediate compounds and the final lipopeptide were characterized by nuclear magnetic resonance (NMR) and mass spectrometry.…”

“…Therefore, a certain focus on the improvement of the efficacy and safety of the delivery vectors that carry the therapeutic genes to a particular target tissue is direly needed. Toward this end, a number of previous reports including ours have demonstrated that amino acid- or peptide head-based lipids help improve biosafety while still providing desired transfection efficiency. − Among several amino acids that have been studied, arginine-based gene delivery systems have been widely accepted for their transfection efficiency . Lipid-based delivery vectors with stimuli-responsive linker moieties that are enzyme-cleavable and pH- or redox-responsive have grabbed the certain interest of researchers for their obvious beneficial results.…”

Effect of Methylation of the Hydrophilic Domain of Tocopheryl Ammonium-Based Lipids on their Nucleic Acid Delivery Properties

“…Furthermore, the serum stability and low toxicity of vitamin E, and the presence of physiological pathways of tocopherol transport to various tissues including brain from blood have led to several investigations on systemic delivery applications. 22 , 23 In recent times, the efficiency of α-tocopherol as a delivery system in vivo for the delivery of nucleic acids has been reported. 15 , 24 It is reported from previous studies that α-tocopherol performed similarly as cholesterol in changing liposomes, i.e., making the liposomes highly protein-induced disruption-resistant, and it as found that this inhibition of protein-induced disruption is more effective with tocopherol compared to cholesterol.…”