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...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-10-01
|
| Series: | Pharmaceuticals |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1424-8247/14/11/1064 |
| _version_ | 1827675764583038976 |
|---|---|
| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T05:10:27Z |
| format | Article |
| id | doaj.art-f0c31434eaa74df2841197714ee41963 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T05:10:27Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-f0c31434eaa74df2841197714ee419632023-11-23T00:54:42ZengMDPI AGPharmaceuticals1424-82472021-10-011411106410.3390/ph14111064Cyclic Peptide-Gadolinium Nanocomplexes as siRNA Delivery ToolsAmir Nasrolahi Shirazi0Muhammad Imran Sajid1Dindyal Mandal2David Stickley3Stephanie Nagasawa4Joshua Long5Sandeep Lohan6Keykavous Parang7Rakesh Kumar Tiwari8Department of Pharmaceutical Sciences, College of Pharmacy, Marshall B. Ketchum University, Fullerton, CA 92831, USACenter for Targeted Drug Delivery, Department of Biomedical and Pharmaceutical Sciences, Harry and Diane Rinker Health Science Campus, Chapman University School of Pharmacy, Irvine, CA 92618, USACenter for Targeted Drug Delivery, Department of Biomedical and Pharmaceutical Sciences, Harry and Diane Rinker Health Science Campus, Chapman University School of Pharmacy, Irvine, CA 92618, USADepartment of Pharmaceutical Sciences, College of Pharmacy, Marshall B. Ketchum University, Fullerton, CA 92831, USADepartment of Pharmaceutical Sciences, College of Pharmacy, Marshall B. Ketchum University, Fullerton, CA 92831, USADepartment of Pharmaceutical Sciences, College of Pharmacy, Marshall B. Ketchum University, Fullerton, CA 92831, USACenter for Targeted Drug Delivery, Department of Biomedical and Pharmaceutical Sciences, Harry and Diane Rinker Health Science Campus, Chapman University School of Pharmacy, Irvine, CA 92618, USACenter for Targeted Drug Delivery, Department of Biomedical and Pharmaceutical Sciences, Harry and Diane Rinker Health Science Campus, Chapman University School of Pharmacy, Irvine, CA 92618, USACenter for Targeted Drug Delivery, Department of Biomedical and Pharmaceutical Sciences, Harry and Diane Rinker Health Science Campus, Chapman University School of Pharmacy, Irvine, CA 92618, USAWe 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.https://www.mdpi.com/1424-8247/14/11/1064siRNA delivery systemscyclic peptidesgadolinium nanoparticlesintracellular transportationnanocomplexes |
| spellingShingle | 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 Pharmaceuticals siRNA delivery systems cyclic peptides gadolinium nanoparticles intracellular transportation nanocomplexes |
| title | 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_short | Cyclic Peptide-Gadolinium Nanocomplexes as siRNA Delivery Tools |
| title_sort | cyclic peptide gadolinium nanocomplexes as sirna delivery tools |
| topic | siRNA delivery systems cyclic peptides gadolinium nanoparticles intracellular transportation nanocomplexes |
| url | https://www.mdpi.com/1424-8247/14/11/1064 |
| work_keys_str_mv | AT amirnasrolahishirazi cyclicpeptidegadoliniumnanocomplexesassirnadeliverytools AT muhammadimransajid cyclicpeptidegadoliniumnanocomplexesassirnadeliverytools AT dindyalmandal cyclicpeptidegadoliniumnanocomplexesassirnadeliverytools AT davidstickley cyclicpeptidegadoliniumnanocomplexesassirnadeliverytools AT stephanienagasawa cyclicpeptidegadoliniumnanocomplexesassirnadeliverytools AT joshualong cyclicpeptidegadoliniumnanocomplexesassirnadeliverytools AT sandeeplohan cyclicpeptidegadoliniumnanocomplexesassirnadeliverytools AT keykavousparang cyclicpeptidegadoliniumnanocomplexesassirnadeliverytools AT rakeshkumartiwari cyclicpeptidegadoliniumnanocomplexesassirnadeliverytools |