Lenvatinib-Loaded Poly(lactic-co-glycolic acid) Nanoparticles with Epidermal Growth Factor Receptor Antibody Conjugation as a Preclinical Approach to Therapeutically Improve Thyroid Cancer with Aggressive Behavior
dc.contributor.author | Revilla, Giovanna | |
dc.contributor.author | Al Qtaish, Nuseibah | |
dc.contributor.author | Caruana, Pablo | |
dc.contributor.author | Sainz Ramos, Myriam | |
dc.contributor.author | López Méndez, Tania Belén | |
dc.contributor.author | Rodriguez, Francisco | |
dc.contributor.author | Paez-Espinosa, Verónica | |
dc.contributor.author | Li, Changda | |
dc.contributor.author | Vallverdú, Núria Fucui | |
dc.contributor.author | Edwards, Maria | |
dc.contributor.author | Moral, Antonio | |
dc.contributor.author | Pérez, José Ignacio | |
dc.contributor.author | Escolà-Gil, Juan Carlos | |
dc.contributor.author | Pedraz Muñoz, José Luis ![]() | |
dc.contributor.author | Gallego Garrido, Idoia | |
dc.contributor.author | Corcoy, Rosa | |
dc.contributor.author | Céspedes, María Virtudes | |
dc.contributor.author | Puras Ochoa, Gustavo | |
dc.contributor.author | Mato, Eugènia | |
dc.date.accessioned | 2023-11-27T18:08:46Z | |
dc.date.available | 2023-11-27T18:08:46Z | |
dc.date.issued | 2023-11-13 | |
dc.identifier.citation | Biomolecules 13(11) : (2023) // Article ID 1647 | es_ES |
dc.identifier.issn | 2218-273X | |
dc.identifier.uri | http://hdl.handle.net/10810/63166 | |
dc.description.abstract | Background: Lenvatinib, a tyrosine kinase inhibitor (TKI) approved for the treatment of progressive and radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC), is associated with significant adverse effects that can be partially mitigated through the development of novel drug formulations. The utilization of nanoparticles presents a viable option, as it allows for targeted drug delivery, reducing certain side effects and enhancing the overall quality of life for patients. This study aimed to produce and assess, both in vitro and in vivo, the cytotoxicity, biodistribution, and therapeutic efficacy of lenvatinib-loaded PLGA nanoparticles (NPs), both with and without decoration using antibody conjugation (cetuximab), as a novel therapeutic approach for managing aggressive thyroid tumors. Methods: Poly(lactic-co-glycolic acid) nanoparticles (NPs), decorated with or without anti-EGFR, were employed as a lenvatinib delivery system. These NPs were characterized for size distribution, surface morphology, surface charge, and drug encapsulation efficiency. Cytotoxicity was evaluated through MTT assays using two cellular models, one representing normal thyroid cells (Nthy-ori 3-1) and the other representing anaplastic thyroid cells (CAL-62). Additionally, an in vivo xenograft mouse model was established to investigate biodistribution and therapeutic efficacy following intragastric administration. Results: The NPs demonstrated success in terms of particle size, polydispersity index (PDI), zeta potential, morphology, encapsulation efficiency, and cetuximab distribution across the surface. In vitro analysis revealed cytotoxicity in both cellular models with both formulations, but only the decorated NPs achieved an ID50 value in CAL-62 cells. Biodistribution analysis following intragastric administration in xenografted thyroid mice demonstrated good stability in terms of intestinal barrier function and tumor accumulation. Both formulations were generally well tolerated without inducing pathological effects in the examined organs. Importantly, both formulations increased tumor necrosis; however, decorated NPs exhibited enhanced parameters related to apoptotic/karyolytic forms, mitotic index, and vascularization compared with NPs without decoration. Conclusions: These proof-of-concept findings suggest a promising strategy for administering TKIs in a more targeted and effective manner. | es_ES |
dc.description.sponsorship | This research was funded by the Spanish “Ministerio de Ciencia, Innovación y Universidades” and “Instituto de Salud Carlos III” through projects FIS PI19/00136 (to J.C.E.–G. and E.M.) and PI20/00770 (to MVC). Additionally, G.R. was granted a PhD fellowship co-financed by “Instituto Salud Carlos III, Madrid, Spain” (PFIS) and Fondo Social Europeo (FSE), grant FI19/00007. P.C. received a PFIS predoctoral contract (FI21/00146), and M.V.C is supported by the Miguel Servet II (CPII20/00007) Program, both from the ISCIII with co-funding from the European Social Fund (ESF Investing in Your Future), Spain. MVC is also part of the RICORS Network, Instituto Salud Carlos III, Madrid, Spain. ME is supported by a pre-doctoral INPhINIT fellowship from La Caixa (2022, B005830). | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | MDPI | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.subject | thyroid | es_ES |
dc.subject | nanoparticles | es_ES |
dc.subject | EGFR | es_ES |
dc.subject | lenvatinib | es_ES |
dc.title | Lenvatinib-Loaded Poly(lactic-co-glycolic acid) Nanoparticles with Epidermal Growth Factor Receptor Antibody Conjugation as a Preclinical Approach to Therapeutically Improve Thyroid Cancer with Aggressive Behavior | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.date.updated | 2023-11-24T14:28:28Z | |
dc.rights.holder | © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). | es_ES |
dc.relation.publisherversion | https://www.mdpi.com/2218-273X/13/11/1647 | es_ES |
dc.identifier.doi | 10.3390/biom13111647 | |
dc.departamentoes | Farmacia y ciencias de los alimentos | |
dc.departamentoeu | Farmazia eta elikagaien zientziak |
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Except where otherwise noted, this item's license is described as © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).