Gold Nanoparticle Aggregates Functionalized with Cyclic RGD Peptides for Targeting and Imaging of Colorectal Cancer Cells

Abstract

The active targeting strategy has emerged as a promising approach to achieve selectivity in nanobiotechnology applications. Peptides are particularly suited as targeting moieties because the multivalent presentation of these small molecules on a nanoparticle provides high avidity for the target. However, to achieve an efficient targeting activity, the presentation of the peptide on the nanostructure has to be supported by an appropriate design. To optimize the targeting to colorectal cancer cells, we have performed a ligand design study of plasmonic nanostructures covered with a cyclic RGD peptide, a known targeting moiety for the α v β 3 integrin. We find that to achieve a good targeting activity, the RGD peptide has to be linked to plasmonic nanostructures through a long PEG chain and a short oligolysine spacer. When the cyclic RGD peptide is directly linked to the PEG chains of the nanostructures, their targeting ability is lost. Molecular dynamics calculations make possible to understand the difference of the peptide organization in two targeted nanosystems, unveiling an effect of the spacer on the orientation of the active component, which very likely positively affects the targeting properties of the investigated plasmonic nanostructures.

Nanoparticles Engineering by Pulsed Laser Ablation in Liquids: Concepts and Applications

“…In particular we obtained a nanostructured system in which a SERS label and an MRI contrast agent based on Gd3+ were present. MRI images of a tumor were obtained for mice injected with the nanostructures together with SERS images, which easily showed the margin of the tumor [182] (see Figure 17b). the Au NP surface, obtained with Molecular Dynamics calculations, show that the presence of the short lysine charged sequence is strategic for obtaining the appropriate exposition of the targeting peptide over the PEG chains, collapsed over the NP surface [172,182].…”

“…MRI images of a tumor were obtained for mice injected with the nanostructures together with SERS images, which easily showed the margin of the tumor [182] (see Figure 17b). the Au NP surface, obtained with Molecular Dynamics calculations, show that the presence of the short lysine charged sequence is strategic for obtaining the appropriate exposition of the targeting peptide over the PEG chains, collapsed over the NP surface [172,182]. SERS signals, as a new approach for the detection of targeting events are much more efficient than the usual fluorescence signals and allow very easy multiplexing measurements because of the very narrow bands that can be recorded for vibrational SERS spectra with respect to the very large bands observed for fluorescence spectra [175].…”

“…In particular we obtained a nanostructured system in which a SERS label and an MRI contrast agent based on Gd3+ were present. MRI images of a tumor were obtained for mice injected with the nanostructures together with SERS images, which easily showed the margin of the tumor [182] (see Figure 17b). These experiments also made it possible to use NPs for photothermal therapy of the tumor, evidencing an increase of the tumor far field measured temperature, after 10 min of irradiation, by 8 degrees which is considered sufficient to start the apoptosis mechanism for the tumor cells.…”

SERRS multiplexing with multivalent nanostructures for the identification and enumeration of epithelial and mesenchymal cells

“…It is worth mentioning that the presence of a plasmonic structure usually suppresses fluorescence signals of molecules close to the nanoparticles (NPs), making background signals negligible. We have already shown that the opportunities given by the SERRS approach can be successfully exploited for specifically identifying prostatic tumor cells expressing prostate specific membrane antigen (PSMA) and prostate stem cell antigen (PSCA) 26 , 31 or other antigens using engineered peptides 25 , 34 , 35 . The functionalization of plasmonic nanostructures with a large number of antibodies (Abs) increases the targeting activity with respect to isolated Abs 36 , 37 .…”

Coarse-Grained Simulation of the Adsorption of Water on Au(111) Surfaces Using a Modified Stillinger–Weber Potential

“…In the last few years, in nanoscience, the use of functionalized nanoparticles with biomolecules has gained a lot of interest, with applications in drug delivery, 1 theranostics, 2 heterogeneous catalysis, 3 and clinical 4 and environmental 5 analyses. Functionalization is possible by using covalently bonded molecules on Au surfaces by means of thiol groups.…”