scFv biofunctionalized nanoparticles to effective and safe targeting of CEA-expressing colorectal cancer cells.
J Nanobiotechnology
; 21(1): 357, 2023 Oct 02.
Article
en En
| MEDLINE
| ID: mdl-37784150
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias Colorrectales
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Nanopartículas
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Anticuerpos de Cadena Única
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
J Nanobiotechnology
Año:
2023
Tipo del documento:
Article
País de afiliación:
Portugal