title: Cyclic peptide-selenium nanoparticles as drug transporters.
abstract: 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-SeNPs) in situ. A physical mixing of the cyclic peptide with SeO3(-2) solution in water generated [W5R4C]-SeNPs via the combination of reducing and capping properties of amino acids in the peptide structure. Transmission electron microscopy (TEM) images showed that [W5R4C]-SeNPs were in the size range of 110-150 nm. Flow cytometry data revealed that a fluorescence-labeled phosphopeptide (F'-PEpYLGLD, where F' = fluorescein) and an anticancer drug (F'-dasatinib) exhibited approximately 25- and 9-times higher cellular uptake in the presence of [W5R4C]-SeNPs than those of F'-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'-PEpYLGLD and F'-dasatinib in the presence of [W5R4C]-SeNPs compared to the parent fluorescence-labeled drug alone in human ovarian adenocarcinoma (SK-OV-3) cells after 2 h of incubation at 37 °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]-SeNPs (50 μM) 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-SeNPs can be potentially used as nanosized delivery tools for negatively charged biomolecules and anticancer drugs.
authors.affiliation: Chao Family Comprehensice Cancer Center, School of Medicine, University of California, Irvine , Shanbrom Hall, 101 The City Drive South, Orange, California 92868, United States.
authors.forename: Amir
authors.initials: A
authors.lastname: Nasrolahi Shirazi
authors.forename: Rakesh K
authors.initials: RK
authors.lastname: Tiwari
authors.forename: Donghoon
authors.initials: D
authors.lastname: Oh
authors.forename: Brian
authors.initials: B
authors.lastname: Sullivan
authors.forename: Anil
authors.initials: A
authors.lastname: Kumar
authors.forename: Yousef A
authors.initials: YA
authors.lastname: Beni
authors.forename: Keykavous
authors.initials: K
authors.lastname: Parang
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D053768:Metal Nanoparticles / Q000737:chemistry*; D046529:Microscopy, Electron, Transmission; D010456:Peptides, Cyclic / Q000737:chemistry*; D012643:Selenium / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D010456:Peptides, Cyclic; D004317:Doxorubicin; D012643:Selenium
keywords: antiproliferative; drug delivery; metal; nanoparticle; selenium