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Gold Nanoparticles Functionalized with RGD‐Semipeptides: A Simple yet Highly Effective Targeting System for α V β 3 Integrins
Author(s) -
Maggi Vito,
Bianchini Francesca,
Portioli Elisabetta,
Peppicelli Silvia,
Lulli Matteo,
Bani Daniele,
Del Sole Roberta,
Zanardi Franca,
Sartori Andrea,
Fiammengo Roberto
Publication year - 2018
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201801823
Subject(s) - bifunctional , colloidal gold , integrin , nanoparticle , biophysics , nanotechnology , internalization , peg ratio , vitronectin , endocytosis , chemistry , ethylene glycol , materials science , receptor , biochemistry , biology , organic chemistry , finance , economics , catalysis
Effective and selective targeting of the α V β 3 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, α V β 3 ‐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.