Delivery of Survivin siRNA Using Cationic Diphenylalanine Vesicles

Guan, Shuwen; Yu, Xiaoxuan; Li, Junyang; Xu, Heng Qiu; Han, Wei; Shi, Guannan; Xu, Jia; Wang, Liping

doi:10.1007/s40242-019-8184-8

Cited by 7 publications

(2 citation statements)

References 24 publications

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“…The numbers of Dip and W residues were varied to determine the optimal balance of hydrophobicity and hydrophilic residues for the maximum cellular uptake. Previously, dipeptides with two phenylalanine amino acids have been reported as an efficient siRNA delivery system with promising prospects for cancer therapy [ 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 ]. To the best of our knowledge, this is the first report of systematic design and evaluation of CPPs containing R and Dip with or without W residues as molecular transporters.…”

Section: Introductionmentioning

confidence: 99%

Amphiphilic Cell-Penetrating Peptides Containing Natural and Unnatural Amino Acids as Drug Delivery Agents

Salehi

Mozaffari

Zoghebi

et al. 2022

Cells

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A series of cyclic peptides, [(DipR)(WR)4], [(DipR)2(WR)3], [(DipR)3(WR)2], [(DipR)4(WR)], and [DipR]5, and their linear counterparts containing arginine (R) as positively charged residues and tryptophan (W) or diphenylalanine (Dip) as hydrophobic residues, were synthesized and evaluated for their molecular transporter efficiency. The in vitro cytotoxicity of the synthesized peptides was determined in human epithelial ovary adenocarcinoma cells (SK-OV-3), human lymphoblast peripheral blood cells (CCRF-CEM), human embryonic epithelial kidney healthy cells (HEK-293), human epithelial mammary gland adenocarcinoma cells (MDA-MB-468), pig epithelial kidney normal cells (LLC-PK1), and human epithelial fibroblast uterine sarcoma cells (MES-SA). A concentration of 5–10 µM and 3 h incubation were selected in uptake studies. The cellular uptake of a fluorescent-labeled phosphopeptide, stavudine, lamivudine, emtricitabine, and siRNA was determined in the presence of peptides via flow cytometry. Among the peptides, [DipR]5 (10 µM) was found to be the most efficient transporter and significantly improved the uptake of F’-GpYEEI, i.e., by approximately 130-fold after 3 h incubation in CCRF-CEM cells. Confocal microscopy further confirmed the improved delivery of fluorescent-labeled [DipR]5 (F’-[K(DipR)5]) alone and F’-GpYEEI in the presence of [DipR]5 in MDA-MB-231 cells. The uptake of fluorescent-labeled siRNA (F’-siRNA) in the presence of [DipR]5 with N/P ratios of 10 and 20 was found to be 30- and 50-fold higher, respectively, compared with the cells exposed to F’-siRNA alone. The presence of endocytosis inhibitors, i.e., nystatin, chlorpromazine, chloroquine, and methyl β-cyclodextrin, did not completely inhibit the cellular uptake of F’-[K(DipR)5] alone or F’-GpYEEI in the presence of [DipR]5, suggesting that a combination of mechanisms contributes to uptake. Circular dichroism was utilized to determine the secondary structure, while transmission electron microscopy was used to evaluate the particle sizes and morphology of the peptides. The data suggest the remarkable membrane transporter property of [DipR]5 for improving the delivery of various small molecules and cell-impermeable negatively charged molecules (e.g., siRNA and phosphopeptide).

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Section: Introductionmentioning

confidence: 99%

Amphiphilic Cell-Penetrating Peptides Containing Natural and Unnatural Amino Acids as Drug Delivery Agents

Salehi

Mozaffari

Zoghebi

et al. 2022

Cells

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show abstract

“…Moreover, we found that FF has low cytotoxicity and high transfection efficiency. 31,32 In this study, we aimed to test if this carrier is selective for tumors. For this purpose, we designed FFPFF, which linked Pluronic® F-127 and the FF sequence through Schiff bond aggregation.…”

Section: Introductionmentioning

confidence: 99%