Design, synthesis and evaluation of RGD peptidomimetic - Gold nanostar conjugates as M21 cell adhesion inhibitors

Riccardo Innocenti; Caterina Dallari; Elena Lenci; Francesco S Pavone; Francesca Bianchini; Caterina Credi; Andrea Trabocchi

doi:10.1016/j.bioorg.2022.105873

Design, synthesis and evaluation of RGD peptidomimetic - Gold nanostar conjugates as M21 cell adhesion inhibitors

Bioorg Chem. 2022 Sep:126:105873. doi: 10.1016/j.bioorg.2022.105873. Epub 2022 May 15.

Authors

Riccardo Innocenti¹, Caterina Dallari², Elena Lenci³, Francesco S Pavone⁴, Francesca Bianchini⁵, Caterina Credi⁶, Andrea Trabocchi⁷

Affiliations

¹ Department of Chemistry "Ugo Schiff", University of Florence, Via della Lastruccia 13, 50019 Sesto Fiorentino, Florence, Italy; European Laboratory for Non-linear Spectroscopy (LENS), University of Florence, Sesto Fiorentino, Florence, Italy.
² European Laboratory for Non-linear Spectroscopy (LENS), University of Florence, Sesto Fiorentino, Florence, Italy; Department of Physics, University of Florence, Sesto Fiorentino, Florence, Italy.
³ Department of Chemistry "Ugo Schiff", University of Florence, Via della Lastruccia 13, 50019 Sesto Fiorentino, Florence, Italy. Electronic address: elena.lenci@unifi.it.
⁴ European Laboratory for Non-linear Spectroscopy (LENS), University of Florence, Sesto Fiorentino, Florence, Italy; National Institute of Optics -National Research Council (CNR-INO), Sesto Fiorentino, Florence, Italy; Department of Physics, University of Florence, Sesto Fiorentino, Florence, Italy.
⁵ Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Viale Morgagni 50, 50134 Florence, Italy.
⁶ European Laboratory for Non-linear Spectroscopy (LENS), University of Florence, Sesto Fiorentino, Florence, Italy; National Institute of Optics -National Research Council (CNR-INO), Sesto Fiorentino, Florence, Italy. Electronic address: credi@lens.unifi.it.
⁷ Department of Chemistry "Ugo Schiff", University of Florence, Via della Lastruccia 13, 50019 Sesto Fiorentino, Florence, Italy. Electronic address: andrea.trabocchi@unifi.it.

PMID: 35598570
DOI: 10.1016/j.bioorg.2022.105873

Abstract

Effective targeting of α_vβ₃ integrin is of high relevance in cancer research as this protein is overexpressed on several types of tumor cells, making such receptor ideal for the development of therapeutics and of diagnostic imaging agents. In this paper, the synthesis of a novel functionalized triazole-based RGD peptidomimetic and its covalent conjugation on pegylated gold nanostars is reported. These highly stable nanoconstructs showed a multivalent effect in binding α_vβ₃ integrin receptors and proved to inhibit M21 cell adhesion at 25 pM concentration. Thanks to their peculiar surface plasmon resonance in the "NIR transparent window", targeted gold nanostars may represent a promising agent for anticancer multi-modality treatments. 2009 Elsevier Ltd. All rights reserved.

Keywords: Bioconjugate chemistry; Cancer; Drug delivery; Integrin; Targeted therapy.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Adhesion
Cell Line, Tumor
Gold
Integrin alphaVbeta3 / metabolism
Integrin beta3
Oligopeptides / pharmacology
Peptidomimetics* / pharmacology

Substances

Integrin alphaVbeta3
Integrin beta3
Oligopeptides
Peptidomimetics
Gold