Cyclic Peptide-Capped Gold Nanoparticles as Drug Delivery Systems

Abstract

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.

Self-assembly of peptides to nanostructures

“…46 We found out that the combination of tryptophan and positively charged amino acids worked as reducing/capping agents and led to the formation of in-situ functionalized metal nanoparticles.…”

Surface Decorated Gold Nanoparticles by Linear and Cyclic Peptides as Molecular Transporters

“…Confocal microscopy revealed the localization of fluorescence-labeled-3TC in the presence of c[KW] 5 -AuNPs mostly in nucleus in SK-OV-3 cells after 1 h. On the other hand, l(KW) 5 -AuNPs delivered fluorescence-labeled-3TC in cytoplasm. Furthermore, c[KW] 4 -AuNPs offered two major advantages over c[RW] 4 -AuNPs that we previously reported 15 . First, the reaction time for the formation of c[KW] 4 -AuNPs (1 h) was significantly shorter compared to that of c[RW] 4 -AuNPs (4-8 h).…”

“…15 Incubation of F′-l(KW) 5 -AuNPs and F′-c[KW] 5 -AuNPs with SK-OV-3 cells showed 3.3- and 4.3-fold higher cellular uptake compared to the corresponding fluorescently-labeled peptides F′-l(KW) 5 and F′-c[KW] 5 , respectively, thus suggesting the formation of P-AuNPs is crucial for the enhanced cellular permeability (Figure 5). FACS results confirmed that F′-c[KW] 5 -AuNPs showed approximately 1.6-fold higher cellular uptake than F′-l(KW) 5 -AuNPs, suggesting that the cyclic nature of the peptide in P-AuNPs contributes to improving the cellular uptake.…”

“…14 Subsequently, it was found that a physical mixture of the cell-penetrating cyclic peptide [WR] 4 and HAuCl 4 led to the formation of peptide-capped gold nanoparticles (P-AuNPs) and enhanced the cellular uptake of drugs significantly. 15 It remains to be determined whether non-cell penetrating peptides can be converted to a nuclear targeting DDS through generation of peptide-AuNPs.…”

Cellular uptake and anti-tumor activity of gemcitabine conjugated with new amphiphilic cell penetrating peptides

“…It has been demonstrated that conjugation of gemcitabine with polypeptide may improve its plasma stability and sustain the drug release profile (Kiew et al, 2010[21]). In recent years, numerous natural and synthetic CPPs, such as Tat, transportan, and polyamino acids (e.g., poly-arginines), were discovered or designed for intracellular delivery of anticancer agents (Gupta et al, 2011[19]; Nasrolahi Shirazi et al, 2013[31]). Among these CPPs, TAT peptide and poly-arginine are the most frequently used for the delivery of various molecules such as proteins, peptides, RNA, therapeutic and imaging compounds into cells (Shirazi et al, 2014[39]; Tsumuraya and Matsushita, 2014[42]).…”