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• W4293230872 abstract "Cimetidine, a histamine-2 (H2) receptor antagonist, has been found to have anticancer properties against a number of cancer-type cells. In this report, we have demonstrated that cimetidine can acts as a hydrophilic domain in cationic lipids and targetable to the gastric system by carrying reporter genes and therapeutic genes through in vitro transfection. Two lipids, namely, Toc-Cim and Chol-Cim consisting cimetidine as the main head group and hydrophobic moieties as alpha-tocopherol or cholesterol, respectively, were designed and synthesized. 1,2-Dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) is a well-known co-lipid employed to produce liposomes as uniform vesicles. The liposomes and lipoplexes were structurally and functionally evaluated for global surface charges and hydrodynamic diameters, and results found that both liposome and lipoplex size and surface charges are optimal to screen the transfection potentials. DNA-binding studies were analyzed as complete binding at all formulated N/P ratios. The liposomes and lipoplexes of both the lipids Toc-Cim and Chol-Cim show minimal cytotoxicity even though at higher concentrations. The results of the transfection experiments revealed that tocopherol-based cationic lipids (Toc-Cim) show finer transfection efficacy with optimized N/P ratios (2:1 and 4:1) in the colon cancer cell line. Toc-Cim lipoplexes show higher cellular uptake compare to Chol-Cim in the colon cancer cell line at 2:1 and 4:1 N/P ratios. Toc-Cim and Chol-Cim lipids showed highly compatible serum, examined up to 50% of the serum concentration. To evaluate the apoptotic cell death in CT-26 cells, exposed to Toc-Cim:p53 and Chol-Cim:p53 lipoplexes at 2:1 N/P ratios, superior results showed with Toc-Cim:p53. An effect of TP53 protein expression in CT-26 cell lines assayed by western blot, transfected with Toc-Cim:p53 and Chol-Cim:p53 lipoplexes, demonstrated the superior efficacy of Toc-Cim. All of the findings suggest that Toc-Cim lipid is relatively secure and is an effective transfection agent to colon cancer gene delivery." @default.
• W4293230872 created "2022-08-27" @default.
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• W4293230872 date "2022-08-25" @default.
• W4293230872 modified "2023-09-24" @default.
• W4293230872 title "Cimetidine-Based Cationic Amphiphiles for In Vitro Gene Delivery Targetable to Colon Cancer" @default.
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• W4293230872 doi "https://doi.org/10.1021/acsomega.2c03777" @default.
• W4293230872 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36092589" @default.
• W4293230872 hasPublicationYear "2022" @default.
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