Selective Anticancer Therapy Based on a HA-CD44 Interaction Inhibitor Loaded on Polymeric Nanoparticles

Autor: José M. Espejo-Román, Belén Rubio-Ruiz, Victoria Cano-Cortés, Olga Cruz-López, Saúl Gonzalez-Resines, Carmen Domene, Ana Conejo-García, Rosario M. Sánchez-Martín
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Pharmaceutics, Vol 14, Iss 4, p 788 (2022)
Druh dokumentu: article
ISSN: 1999-4923
DOI: 10.3390/pharmaceutics14040788
Popis: Hyaluronic acid (HA), through its interactions with the cluster of differentiation 44 (CD44), acts as a potent modulator of the tumor microenvironment, creating a wide range of extracellular stimuli for tumor growth, angiogenesis, invasion, and metastasis. An innovative antitumor treatment strategy based on the development of a nanodevice for selective release of an inhibitor of the HA-CD44 interaction is presented. Computational analysis was performed to evaluate the interaction of the designed tetrahydroisoquinoline-ketone derivative (JE22) with CD44 binding site. Cell viability, efficiency, and selectivity of drug release under acidic conditions together with CD44 binding capacity, effect on cell migration, and apoptotic activity were successfully evaluated. Remarkably, the conjugation of this CD44 inhibitor to the nanodevice generated a reduction of the dosis required to achieve a significant therapeutic effect.
Databáze: Directory of Open Access Journals
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