Bis‐Thioether‐Containing Lipid Chains in Cationic Amphiphiles: Physicochemical Properties and Applications in Gene Delivery

Abstract

Cationic amphiphiles featuring two thioether functions in each lipid chain of bicatenar cationic amphiphiles are herein reported for the first time. The physico-chemical properties and transfection abilities of these new amphiphiles were compared with those of already reported analogues featuring either (i) saturated, (ii) unsaturated or (iii) mono-thioether containing lipid chains. The homogeneity of the series of new compounds allowed to clearly underscore the effect of bis-thioether containing lipid chains. This study shows that besides previous strategies based on unsaturation or ramification, the incorporation of two thioether functions per lipid chain constitutes an original complementary alternative to tune the supramolecular properties of amphiphilic compounds. The potential of this strategy was evaluated in the context of gene delivery and report that two cationic amphiphiles (i.e. 4a and 4b) can be proposed as new efficient transfection reagents.

Antibody-Conjugated Vitamin E-Derived Liposomes for Targeted Gene Transfer

“…It has been well established that p53 gene therapy activates proapoptotic machinery by provoking the G 0 /G 1 and G 2 /M cell cycle arrest. ,, With the aim of specifically incorporating a plasmid encoding for this tumor suppressor protein and restoring the apoptotic machinery in hepatocellular carcinoma, the anti-LDLr-tagged TH8S liposomes were used for the transfection of pCEP4-p53. Inhibition of cell proliferation, observed from the MTT Assay, showed that the tagged liposomes were able to deliver the plasmid efficiently in HepG2 and Huh7 cells ( Figure A).…”

“…FT-IR (neat, cm Preparation of Maleimide-Functionalized Liposomes. The maleimide-functionalized tocopherol, TME (7), was dissolved in chloroform and mixed with chloroform solution of TH8S 19 maintaining 5 and 10 mol % amounts in two autoclaved Wheaton glass vials for each composition. For DOPE formulations, the helper lipid DOPE, dissolved in chloroform, was added in one of the vials of each group maintaining a molar ratio of 2:1 with respect to TH8S.…”

“…Being a major contributor to cancer-related mortality over the globe, hepatocellular carcinoma (HCC) demands a fast and efficient remediation. With the increasing importance of liposomes as delivery agents for cancer gene therapy, newer and more promising approaches have been devised in order to achieve a therapeutically active level of transfection. − Cationic gemini lipids have been established as reliable, safe, and efficient gene delivery carriers. − However, successful translation of liposome-mediated gene therapeutic applications from the laboratory to the patient’s bedside requires significant advancements, particularly for the improvement of their biodistribution and in vivo targeting, along with immunomodulation. − …”