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Cyclic Peptide-Gadolinium Nanoparticles for Enhanced Intracellular Delivery

Authors :
Amir Nasrolahi Shirazi
Shang Eun Park
Shirin Rad
Luiza Baloyan
Dindyal Mandal
Muhammad Imran Sajid
Ryley Hall
Sandeep Lohan
Khalid Zoghebi
Keykavous Parang
Rakesh Kumar Tiwari
Source :
Pharmaceutics, Vol 12, Iss 9, p 792 (2020)
Publication Year :
2020
Publisher :
MDPI AG, 2020.

Abstract

A cyclic peptide containing one cysteine and five alternating tryptophan and arginine amino acids [(WR)5C] was synthesized using Fmoc/tBu solid-phase methodology. The ability of the synthesized cyclic peptide to produce gadolinium nanoparticles through an in situ one-pot mixing of an aqueous solution of GdCl3 with [(WR)5C] peptide solution was evaluated. Transmission electron microscopy showed the formed peptide-Gd nanoparticles in star-shape morphology with a size of ~250 nm. Flow cytometry investigation showed that the cellular uptake of a cell-impermeable fluorescence-labeled phosphopeptide (F′-GpYEEI, where F′ = fluorescein) was approximately six times higher in the presence of [(WR)5C]-Gd nanoparticles than those of F′-GpYEEI alone in human leukemia adenocarcinoma (CCRF-CEM) cells after 2 h incubation. The antiproliferative activities of cisplatin and carboplatin (5 µM) were increased in the presence of [(WR)5C]-GdNPs (50 μM) by 41% and 18%, respectively, after 72-h incubation in CCRF-CEM cells. The intracellular release of epirubicin, an anticancer drug, from the complex showed that 15% and 60% of the drug was released intracellularly within 12 and 48 h, respectively. This report provides insight about using a non-toxic MRI agent, gadolinium nanoparticles, for the delivery of various types of molecular cargos.

Details

Language :
English
ISSN :
19994923
Volume :
12
Issue :
9
Database :
Directory of Open Access Journals
Journal :
Pharmaceutics
Publication Type :
Academic Journal
Accession number :
edsdoj.9ab1a5d0e6ec459f8de2689aac5dd26e
Document Type :
article
Full Text :
https://doi.org/10.3390/pharmaceutics12090792