Cyclic Peptide鈥揝elenium Nanoparticles as Drug Transporters
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- 作者：Amir Nasrolahi Shirazi ; Rakesh K. Tiwari ; Donghoon Oh ; Brian Sullivan ; Anil Kumar ; Yousef A. Beni ; Keykavous Parang
- 刊名：Molecular Pharmaceutics
- 出版年：2014
- 出版时间：October 6, 2014
- 年：2014
- 卷：11
- 期：10
- 页码：3631-3641
- 全文大小：625K
- ISSN：1543-8392
文摘
A cyclic peptide composed of five tryptophan, four arginine, and one cysteine [W5R4C] was synthesized. The peptide was evaluated for generating cyclic peptide-capped selenium nanoparticles (CP鈥揝eNPs) in situ. A physical mixing of the cyclic peptide with SeO3鈥? solution in water generated [W5R4C]鈥揝eNPs via the combination of reducing and capping properties of amino acids in the peptide structure. Transmission electron microscopy (TEM) images showed that [W5R4C]鈥揝eNPs were in the size range of 110鈥?50 nm. Flow cytometry data revealed that a fluorescence-labeled phosphopeptide (F鈥?PEpYLGLD, where F鈥?= fluorescein) and an anticancer drug (F鈥?dasatinib) exhibited approximately 25- and 9-times higher cellular uptake in the presence of [W5R4C]鈥揝eNPs than those of F鈥?PEpYLGLD and dasatinib alone in human leukemia (CCRF-CEM) cells after 2 h of incubation, respectively. Confocal microscopy also exhibited higher cellular delivery of F鈥?PEpYLGLD and F鈥?dasatinib in the presence of [W5R4C]鈥揝eNPs compared to the parent fluorescence-labeled drug alone in human ovarian adenocarcinoma (SK-OV-3) cells after 2 h of incubation at 37 掳C. The antiproliferative activities of several anticancer drugs doxorubicin, gemcitabine, clofarabine, etoposide, camptothecin, irinotecan, epirubicin, fludarabine, dasatinib, and paclitaxel were improved in the presence of [W5R4C]鈥揝eNPs (50 渭M) by 38%, 49%, 36%, 36%, 31%, 30%, 30%, 28%, 24%, and 17%, respectively, after 48 h incubation in SK-OV-3 cells. The results indicate that CP鈥揝eNPs can be potentially used as nanosized delivery tools for negatively charged biomolecules and anticancer drugs.
<h4>Keywords: h4> antiproliferative; drug delivery; metal; nanoparticle; selenium
<h4>Keywords: h4> antiproliferative; drug delivery; metal; nanoparticle; selenium