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Issue 42, 2017
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In vitro/in vivo “peeling” of multilayered aminocarboxylate gold nanoparticles evidenced by a kinetically stable 99mTc-label†

Francisco Silva,a   Lurdes Gano,a   Maria Paula Cabral Campello,a   Rosa Marques, ORCID logo a   Isabel Prudêncio,a   Ajit Zambre,b   Anandhi Upendran,c   António Paulo ORCID logo *a  and  Raghuraman Kannan*bd  
Author affiliations

* Corresponding authors

a Centro de Ciências e Tecnologias Nucleares, Instituto Superior Técnico, Universidade de Lisboa, Estrada Nacional 10, Km 139.7, 2695-066 Bobadela LRS, Portugal
E-mail: apaulo@ctn.tecnico.ulisboa.pt

b Department of Radiology, University of Missouri-Columbia, Columbia, Missouri-65212, USA

c Institute of Clinical and Translational Science, School of Medicine, University of Missouri-Columbia, Columbia, Missouri-65212, USA

d Department of BioEngineering, University of Missouri-Columbia, Columbia, Missouri-65212, USA
E-mail: kannanr@health.missouri.edu

Abstract

A thiolated bombesin peptide was conjugated to Au-DTDTPA nanoconstructs to obtain BBN-Au-DTDTPA targeted to the gastrin releasing peptide receptor (GRPr). Different analytical techniques showed that this conjugate shares similar physico-chemical properties with Au-DTDTPA; HPLC and XPS analyses corroborated the attachment of the bioactive peptide to the AuNPs surface. Competitive binding assays in PC3 cancer cells showed that these BBN-containing AuNPs have high affinity for GRPr. BBN-Au-DTDTPA was successfully radiolabeled with 99mTc and showed high in vitro stability towards different biological media and substrates, except for glutathione (GSH). In vitro and in vivo studies, based on gamma-counting (99mTc content) and neutron activation analysis (Au content), indicated the release of the DTDTPA coating from the AuNPs. Probably, the “peeling” of the layered-aminocarboxylate coating is GSH-mediated and involves the cleavage of the DTDTPA disulfide bonds and/or Au–S bonds. These results render BBN-Au-DTDTPA an interesting platform deserving further evaluation in target-specific GSH-mediated drug delivery.

Graphical abstract: In vitro/in vivo “peeling” of multilayered aminocarboxylate gold nanoparticles evidenced by a kinetically stable 99mTc-label

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Article information

https://doi.org/10.1039/C7DT00864C
Submitted
09 Mar 2017
Accepted
24 Apr 2017
First published
24 Apr 2017
Dalton Trans., 2017,46, 14572-14583
Article type
Paper
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In vitro/in vivo “peeling” of multilayered aminocarboxylate gold nanoparticles evidenced by a kinetically stable 99mTc-label

F. Silva, L. Gano, M. P. Cabral Campello, R. Marques, I. Prudêncio, A. Zambre, A. Upendran, A. Paulo and R. Kannan, Dalton Trans., 2017, 46, 14572
DOI: 10.1039/C7DT00864C

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