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scFv biofunctionalized nanoparticles to effective and safe targeting of CEA-expressing colorectal cancer cells

Silveira, Maria Jose; Martins, Claudia; Cruz, Tania; Castro, Flavia; Amorim-Costa, Angela; Chester, Kerry; Oliveira, Maria Jose; (2023) scFv biofunctionalized nanoparticles to effective and safe targeting of CEA-expressing colorectal cancer cells. Journal of Nanobiotechnology , 21 (1) , Article 357. 10.1186/s12951-023-02126-4. Green open access

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Abstract

Colorectal cancer (CRC) is one of the deadliest cancers worldwide, with the 5 year survival rate in metastatic cases limited to 12%. The design of targeted and effective therapeutics remains a major unmet clinical need in CRC treatment. Carcinoembryonic antigen (CEA), a glycoprotein overexpressed in most colorectal tumors, may constitute a promising molecule for generating novel CEA-targeted therapeutic strategies for CRC treatment. Here, we developed a smart nanoplatform based on chemical conjugation of an anti-CEA single-chain variable fragment (scFv), MFE-23, with PLGA-PEG polymers to deliver the standard 5-Fluorouracil (5-FU) chemotherapy to CRC cells. We confirmed the specificity of the developed CEA-targeted NPs on the internalization by CEA-expressing CRC cells, with an enhance of threefold in the cell uptake. Additionally, CEA-targeted NPs loaded with 5-FU induced higher cytotoxicity in CEA-expressing cells, after 24 h and 48 h of treatment, reinforcing the specificity of the targeted NPs. Lastly, the safety of CEA-targeted NPs loaded with 5-FU was evaluated in donor-isolated macrophages, with no relevant impact on their metabolic activity nor polarization. Altogether, this proof of concept supports the CEA-mediated internalization of targeted NPs as a promising chemotherapeutic strategy for further investigation in different CEA-associated cancers and respective metastatic sites.Authors: Please confirm if the author names are presented accurately and in the correct sequence (given name, middle name/initial, family name). Author 1 Given name: [Maria José] Last name [Silveira]. Author 7 Given name: [Maria José] Last name [Oliveira]. Also, kindly confirm the details in the metadata are correctokAffiliations: Please check and confirm that the authors and their respective affiliations have been correctly identified and amend if necessary.ok Graphical Abstract: [Figure not available: see fulltext.]

Type: Article
Title: scFv biofunctionalized nanoparticles to effective and safe targeting of CEA-expressing colorectal cancer cells
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1186/s12951-023-02126-4
Publisher version: http://dx.doi.org/10.1186/s12951-023-02126-4
Language: English
Additional information: Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
Keywords: Science & Technology, Life Sciences & Biomedicine, Biotechnology & Applied Microbiology, Nanoscience & Nanotechnology, Science & Technology - Other Topics, Cancer therapy, Carcinoembryonic antigen, Drug delivery, Nanomedicine, Single-chain variable fragment functionalization, Targeted therapies, FV ANTIBODY MFE-23, PLGA NANOPARTICLES, ANTITUMOR-ACTIVITY, ANTIGEN, 5-FLUOROURACIL, MACROPHAGES, INTERNALIZATION, BINDING, NMR
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
URI: https://discovery.ucl.ac.uk/id/eprint/10187863
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