Article In: orcid, cienciavitae, scopus

Interrogating the Role of Receptor-Mediated Mechanisms: Biological Fate of Peptide-Functionalized Radiolabeled Gold Nanoparticles in Tumor Mice

Bioconjugate Chemistry

Silva, F.; Zambre, A.; Paulo, Antonio — 2016 — ACS Publications

Key information

Authors:

Silva, F.; Zambre, A.; Campello, M.P.C. (Maria Paula Cordeiro Crespo Cabral Campello Aboim de Barros); Gano, L. (Maria de Lurdes Barrela Patrício Gano); Santos, I.; Ferraria, A.M. (Ana Maria da Conceição Ferraria); Ferreira, M.J. (Maria João Gomes Ferreira); et al; Paulo, Antonio (António Manuel Rocha Paulo)

Published in

04/20/2016

Abstract

To get a better insight on the transport mechanism of peptide-conjugated nanoparticles to tumors, we performed in vivo biological studies of bombesin (BBN) peptide functionalized gold nanoparticles (AuNPs) in human prostate tumor bearing mice. Initially, we sought to compare AuNPs with thiol derivatives of acyclic and macrocyclic chelators of DTPA and DOTA types. The DTPA derivatives were unable to provide a stable coordination of 67Ga, and therefore, the functionalization with the BBN analogues was pursued for the DOTA-containing AuNPs. The DOTA-coated AuNPs were functionalized with BBN[7–14] using a unidentate cysteine group or a bidentate thioctic group to attach the peptide. AuNPs functionalized with thioctic-BBN displayed the highest in vitro cellular internalization (≈ 25%, 15 min) in gastrin releasing peptide (GRP) receptor expressing cancer cells. However, these results fail to translate to in vivo tumor uptake. Biodistribution studies following intravenous (IV) and intraperitoneal (IP) administration of nanoconjugates in tumor bearing mice indicated that the presence of BBN influences to some degree the biological profile of the nanoconstructs. For IV administration, the receptor-mediated pathway appears to be outweighed by the EPR effect. By contrast, in IP administration, it is reasoned that the GRPr-mediated mechanism plays a role in pancreas uptake.

Publication details

Authors in the community:

Publication version

AO - Author's Original

Publisher

ACS Publications

Link to the publisher's version

https://pubs.acs.org/bc

Title of the publication container

Bioconjugate Chemistry

First page or article number

1153

Last page

1164

Volume

27

Issue

4

DOI

10.1021/acs.bioconjchem.6b00102

WoS (Web of Science)

WOS:000374812600033

Fields of Science and Technology (FOS)

chemical-sciences - Chemical sciences

Publication language (ISO code)

eng - English

Alternative identifier (URI)

http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000374812600033&KeyUID=WOS:000374812600033

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