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

Theactivetargetingstrategyhasemergedasapromising approach to achieve selectivity in nanobiotechnologyapplications. Peptides are particularly suited as targeting moietiesbecause the multivalent presentation of these small molecules on ananoparticle provides high avidity for the target. However, to achievean efficient targeting activity, the presentation of the peptide on thenanostructure has to be supported by an appropriate design. Tooptimize the targeting to colorectal cancer cells, we have performed aligand design study of plasmonic nanostructures covered with a cyclicRGD peptide, a known targeting moiety for theαvβ3-integrin. Wefindthat to achieve a good targeting activity, the RGD peptide has to belinked to plasmonic nanostructures through a long PEG chain and ashort oligolysine spacer. When the cyclic RGD peptide is directly linked to the PEG chains of the nanostructures, their targetingability is lost. Molecular dynamics calculations make possible to understand the difference of the peptide organization in twotargeted nanosystems, unveiling an effect of the spacer on the orientation of the active component, which very likely positivelyaffects the targeting properties of the investigated plasmonic nanostructures.