Cyclic Peptide-Gadolinium Nanocomplexes as siRNA Delivery Tools
We have recently reported that a cyclic peptide containing five tryptophan, five arginine, and one cysteine amino acids [(WR)<sub>5</sub>C], was able to produce peptide-capped gadolinium nanoparticles, [(WR)<sub>5</sub>C]-GdNPs, in the range of 240 to 260 nm upon mixing with...
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| Autores principales: | , , , , , , , , |
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| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
MDPI AG
2021
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/f0c31434eaa74df2841197714ee41963 |
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| Sumario: | We have recently reported that a cyclic peptide containing five tryptophan, five arginine, and one cysteine amino acids [(WR)<sub>5</sub>C], was able to produce peptide-capped gadolinium nanoparticles, [(WR)<sub>5</sub>C]-GdNPs, in the range of 240 to 260 nm upon mixing with an aqueous solution of GdCl<sub>3</sub>. Herein, we report [(WR)<sub>5</sub>C]-GdNPs as an efficient siRNA delivery system. The peptide-based gadolinium nanoparticles (50 µM) did not exhibit significant cytotoxicity (~93% cell viability at 50 µM) in human leukemia T lymphoblast cells (CCRF-CEM) and triple-negative breast cancer cells (MDA-MB-231) after 48 h. Fluorescence-activated cell sorting (FACS) analysis indicated that the cellular uptakes of Alexa-488-labeled siRNA were found to be enhanced by more than 10 folds in the presence of [(WR)<sub>5</sub>C]-GdNPs compared with siRNA alone in CCRF-CEM and MDA-MB-231 cells after 6 h of incubation at 37 °C. The gene silencing efficacy of the nanoparticles was determined via the western blot technique using an over-expressed gene, STAT-3 protein, in MDA-MB-231 cells. The results showed ~62% reduction of STAT-3 was observed in MDA-MB-231 with [(WR)<sub>5</sub>C]-GdNPs at N/P 40. The integrity of the cellular membrane of CCRF-CEM cells was found to be intact when incubated with [(WR)<sub>5</sub>C]-Gd nanoparticles (50 µM) for 2 h. Confocal microscopy reveals higher internalization of siRNA in MDA-MB-231 cells using [(WR)<sub>5</sub>C]-GdNPs at N/P 40. These results provided insight about the use of the [(WR)<sub>5</sub>C]-GdNPs complex as a potent intracellular siRNA transporter that could be a nontoxic choice to be used as a transfection agent for nucleic-acid-based therapeutics. |
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