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  3. Targeted Tumor Microenvironment Delivery of Floxuridine Prodrug via Soluble Silica Nanoparticles in Malignant Melanoma as a Model for Aggressive Cancer Treatment.

Targeted Tumor Microenvironment Delivery of Floxuridine Prodrug via Soluble Silica Nanoparticles in Malignant Melanoma as a Model for Aggressive Cancer Treatment.

Fecha de publicación: Fecha Ahead of Print:

Autores de IDIVAL

Autores ajenos al IDIVAL

  • Domínguez A
  • Navarro N
  • Márquez-López A
  • Aviñó A
  • Eritja R
  • Fàbrega C
  • García-Hevia L

Unidades

Abstract

Malignant melanoma presents a significant challenge in oncology due to its aggressive nature and high metastatic potential. Conventional systemic treatments often fail to effectively reach tumor sites, limiting their therapeutic impact. This study introduces a groundbreaking triple-strategy approach for treating malignant melanoma. A novel prodrug, an oligonucleotide, comprising 10 units of Floxuridine (5-fluoro-2'-deoxyuridine) (FdU) nucleoside antimetabolites are developed, to enhance half-life and reduce rapid metabolism. Encapsulated in soluble colloidal silica nanoparticles, this compound is protected and directed toward tumor neovasculature precursor endothelial cell receptors, ensuring local delivery. The strategy focuses on releasing the prodrug in the tumor microenvironment, aiming to eradicate both melanoma cells and their supportive structures. Efficacy is demonstrated in cell culture studies and preclinical models of malignant melanoma, showing a remarkable 50% reduction in tumor size after just three intravenous treatments. These findings underscore the transformative potential of targeting endothelial cell membrane proteins for drug delivery. This study paves the way for innovative targeted therapies, promising significant advancements in treatment strategies and improves outcomes for patients with metastatic cancers.

© 2025 Wiley-VCH GmbH.

Datos de la publicación

ISSN/ISSNe:
1613-6810, 1613-6829

SMALL  Wiley - V C H Verlag GmbbH & Co.

Tipo:
Article
Páginas:
2407752-2407752
PubMed:
40259607

Citas Recibidas en Web of Science: 2

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Keywords

  • TEM8; VEGF receptor; malignant melanoma; silica nanoparticles; targeted delivery; therapeutic oligonucleotide; tumor neovasculature

Campos de Estudio

Financiación

DTS24/000237
European Union FEDER funds
Gobierno Regional de Cantabria
IDIVAL (AR IDI-020-022)
IDIVAL (PRE2021-097856)
INNVAL21/19
INSTITUTO DE SALUD CARLOS III. (PI23/00261)
NEXTVAL 22/12
PI22/00030
Spanish Ministerio de Ciencia e Innovacion (PID2020-118145RB-I00)
Spanish Ministerio de Ciencia e Innovacion (TED2021-129248B-100)
TED2021-129248

Proyectos asociados

Nuevos nanoportadores dirigidos para el tratamiento y el seguimiento de la metástasis

Investigador Principal: LORENA GARCÍA HEVIA

PI23/00261 . INSTITUTO DE SALUD CARLOS III. . 2024

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