Gold Nanoparticles Functionalized with RGD-Semipeptides: A Simple yet Highly Effective Targeting System for αV β3 Integrins.
Vito MaggiFrancesca BianchiniElisabetta PortioliSilvia PeppicelliMatteo LulliDaniele BaniRoberta Del SoleFranca ZanardiAndrea SartoriRoberto FiammengoPublished in: Chemistry (Weinheim an der Bergstrasse, Germany) (2018)
Effective and selective targeting of the αV β3 integrin subtype is of high relevance in cancer research for the development of therapeutic systems with improved efficacy and of diagnostic imaging probes. We report here a new class of highly selective, αV β3 -targeted gold nanoparticles (AuNPs), which carry cyclic 4-aminoproline-RGD semipeptides (cAmpRGD) as the targeting moiety immobilized at low surface density on the poly(ethylene glycol) (PEG)-based nanoparticle coating. We show that these nanoparticles are potent inhibitors of the integrin-mediated melanoma tumor cell adhesion to vitronectin and are selectively internalized via receptor-mediated endocytosis. Furthermore, we have developed bifunctional cAmpRGD-functionalized AuNPs by conjugation of a fluorophore (FAM or TAMRA) to a separate set of reactive groups on the PEG-based coating. These bifunctional AuNPs not only recapitulate the binding properties of cAmpRGD-AuNPs but also can be visualized via confocal laser microscopy, allowing direct observation of nanoparticle internalization. The peculiar molecular design of these nanoparticles and their precisely defined architecture at the molecular level accounts for their selective integrin binding with very low nonspecific background.
Keyphrases
- cell adhesion
- gold nanoparticles
- cancer therapy
- single molecule
- drug delivery
- high resolution
- optical coherence tomography
- quantum dots
- reduced graphene oxide
- cell migration
- small molecule
- dna binding
- highly efficient
- binding protein
- squamous cell carcinoma
- ionic liquid
- living cells
- raman spectroscopy
- childhood cancer