Xu, RuixueMartínez Bosch, NeusRivera Hueto, FranciscoMulens-Arias, VladimirRubio Moscardó, FannyConesa, José JavierNavarro, PilarVicente García, Rubén, 1978-Rivera Gil, Pilar, 1976-2024-11-152024-11-152024Xu R, Martinez-Bosch N, Rivera-Hueto F, Mulens-Arias V, Rubio-Moscardo F, Conesa JJ, et al. Validation of ZIP4 as a tumour-associated antigen for nanotargeting. J Drug Target. 2024 Oct 1:1-13. DOI: 10.1080/1061186X.2024.24057111061-186Xhttp://hdl.handle.net/10230/68699Data de publicació electrònica: 01-10-2024Pancreatic ductal adenocarcinoma remains a highly aggressive and untreatable cancer. There is a need to develop a new PDAC-associated antigen-targeting drug delivery system to tackle this disease. We validated choosing ZIP4 as a putative target in PDAC theranostics. We developed a nanosystem composed of a fluorescent polystyrene core coated with gold nanoparticles onto which a ZIP4-specific polyclonal antibody is attached. The polystyrene core's fluorescence properties allow the nanosystem tracking by intravital imaging. We also developed two ZIP4-expressing cell lines by stably transfecting HEK293 and RWP1 cells with a ZIP4-coding plasmid that simultaneously provides cells with puromycin resistance. We studied the cell internalisation of the as-synthesised nanoparticles and demonstrated that ZIP4-expressing HEK293 and ZIP4-expressing RWP1 cells tended to take up more ZIP4-targeting nanoparticles. Moreover, we observed that ZIP4-targeting nanoparticles accumulated more in ZIP4-expressing HEK293 and RWP1 tumours when injected intravenously in a subcutaneous xenograft and an orthotopic in vivo model, respectively. Furthermore, the administration of these nanoparticles did not induce any significant systemic toxicity as determined by histological analysis of all organs. Altogether, these results provide the first evidence of the feasibility of using a ZIP4-targeting nanosystem further to design efficient therapeutic and diagnostic tools for PDAC.application/pdfeng© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent.info:eu-repo/semantics/articlehttp://dx.doi.org/10.1080/1061186X.2024.2405711Molecular targetingZIP4BiodistributionDrug delivery nanosystemsHistopathological analysisPancreatic ductal adenocarcinoma (PDAC)info:eu-repo/semantics/openAccess