Cyclic Peptide-Capped Gold Nanoparticles as Drug Delivery Systems
| Autor: | Keykavous Parang, Dindyal Mandal, Rakesh Tiwari, Liangran Guo, Wei Lu, Amir Nasrolahi Shirazi |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Arginine
Cell Survival Stereochemistry Metal Nanoparticles Pharmaceutical Science Peptides Cyclic Flow cytometry Drug Delivery Systems Cell Line Tumor Drug Discovery medicine Humans chemistry.chemical_classification Microscopy Confocal Aqueous solution medicine.diagnostic_test Chemistry Tryptophan Flow Cytometry Combinatorial chemistry Cyclic peptide Microscopy Fluorescence Differential interference contrast microscopy Colloidal gold Drug delivery Molecular Medicine Gold |
| Zdroj: | Molecular Pharmaceutics. 10:500-511 |
| ISSN: | 1543-8392 1543-8384 |
| DOI: | 10.1021/mp300448k |
| Popis: | A number of cyclic peptides were synthesized and evaluated as simultaneous reducing and capping agents for generation of cyclic peptide-capped gold nanoparticles (CP-AuNPs). Among them, direct dissolution of cyclic peptides containing alternate arginine and tryptophan [WR](n) (n = 3-5) into an aqueous solution of AuCl(4)(-) led to the formation of CP-AuNPs, through the reducing activity of tryptophan residues and attraction of positively charged arginine residues toward chloroaurate anions in the reaction environment. Differential interference contrast microscopy of fluorescence-labeled lamivudine in the presence of [WR](4)-capped AuNPs showed significantly higher cellular delivery of antiviral drug versus that of parent drug alone. Flow cytometry studies also showed that the cellular uptake of fluorescence-labeled lamivudine, emtricitabine, and stavudine was significantly enhanced in human ovarian adenocarcinoma (SK-OV-3) cells in the presence of [WR](4)-AuNPs. For example, fluorescence labeled lamivudine-loaded [WR](4)-AuNPs exhibited approximately 12- and 15-times higher cellular uptake than that of fluorescence labeled lamivudine alone in CCRF-CEM cells and SK-OV-3 cells, respectively. Confocal microscopy revealed that the presence of the [WR](4)-AuNPs enhanced the retention and nuclear localization of doxorubicin in SK-OV-3 cells after 24 h. These data suggest that these complexes can be used as potential noncovalent prodrugs for delivery of antiviral and anticancer agents. |
| Databáze: | OpenAIRE |
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