Cyclic Peptide-Gadolinium Nanoparticles for Enhanced Intracellular Delivery

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 solutio...

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Veröffentlicht in:Pharmaceutics 2020-08, Vol.12 (9), p.792
Hauptverfasser: Shirazi, Amir Nasrolahi, Park, Shang Eun, Rad, Shirin, Baloyan, Luiza, Mandal, Dindyal, Sajid, Muhammad Imran, Hall, Ryley, Lohan, Sandeep, Zoghebi, Khalid, Parang, Keykavous, Tiwari, Rakesh Kumar
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Sprache:eng
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Zusammenfassung: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.
ISSN:1999-4923
1999-4923
DOI:10.3390/pharmaceutics12090792