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:	Amir Nasrolahi Shirazi, Muhammad Imran Sajid, Dindyal Mandal, David Stickley, Stephanie Nagasawa, Joshua Long, Sandeep Lohan, Keykavous Parang, Rakesh Kumar Tiwari
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	siRNA delivery systems cyclic peptides gadolinium nanoparticles intracellular transportation nanocomplexes Medicine R Pharmacy and materia medica RS1-441
Acceso en línea:	https://doaj.org/article/f0c31434eaa74df2841197714ee41963
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spelling	oai:doaj.org-article:f0c31434eaa74df2841197714ee419632021-11-25T18:39:02ZCyclic Peptide-Gadolinium Nanocomplexes as siRNA Delivery Tools10.3390/ph141110641424-8247https://doaj.org/article/f0c31434eaa74df2841197714ee419632021-10-01T00:00:00Zhttps://www.mdpi.com/1424-8247/14/11/1064https://doaj.org/toc/1424-8247We 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.Amir Nasrolahi ShiraziMuhammad Imran SajidDindyal MandalDavid StickleyStephanie NagasawaJoshua LongSandeep LohanKeykavous ParangRakesh Kumar TiwariMDPI AGarticlesiRNA delivery systemscyclic peptidesgadolinium nanoparticlesintracellular transportationnanocomplexesMedicineRPharmacy and materia medicaRS1-441ENPharmaceuticals, Vol 14, Iss 1064, p 1064 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	siRNA delivery systems cyclic peptides gadolinium nanoparticles intracellular transportation nanocomplexes Medicine R Pharmacy and materia medica RS1-441
spellingShingle	siRNA delivery systems cyclic peptides gadolinium nanoparticles intracellular transportation nanocomplexes Medicine R Pharmacy and materia medica RS1-441 Amir Nasrolahi Shirazi Muhammad Imran Sajid Dindyal Mandal David Stickley Stephanie Nagasawa Joshua Long Sandeep Lohan Keykavous Parang Rakesh Kumar Tiwari Cyclic Peptide-Gadolinium Nanocomplexes as siRNA Delivery Tools
description	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.
format	article
author	Amir Nasrolahi Shirazi Muhammad Imran Sajid Dindyal Mandal David Stickley Stephanie Nagasawa Joshua Long Sandeep Lohan Keykavous Parang Rakesh Kumar Tiwari
author_facet	Amir Nasrolahi Shirazi Muhammad Imran Sajid Dindyal Mandal David Stickley Stephanie Nagasawa Joshua Long Sandeep Lohan Keykavous Parang Rakesh Kumar Tiwari
author_sort	Amir Nasrolahi Shirazi
title	Cyclic Peptide-Gadolinium Nanocomplexes as siRNA Delivery Tools
title_short	Cyclic Peptide-Gadolinium Nanocomplexes as siRNA Delivery Tools
title_full	Cyclic Peptide-Gadolinium Nanocomplexes as siRNA Delivery Tools
title_fullStr	Cyclic Peptide-Gadolinium Nanocomplexes as siRNA Delivery Tools
title_full_unstemmed	Cyclic Peptide-Gadolinium Nanocomplexes as siRNA Delivery Tools
title_sort	cyclic peptide-gadolinium nanocomplexes as sirna delivery tools
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/f0c31434eaa74df2841197714ee41963
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Cyclic Peptide-Gadolinium Nanocomplexes as siRNA Delivery Tools

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