Selective Anticancer Therapy Based on a HA-CD44 Interaction Inhibitor Loaded on Polymeric Nanoparticles
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
Affiliations
José M. Espejo-Román
Department of Medicinal and Organic Chemistry and Excellence Research Unit of Chemistry Applied to Biomedicine and the Environment, Faculty of Pharmacy, Campus Cartuja s/n, University of Granada, 18071 Granada, Spain
Belén Rubio-Ruiz
Department of Medicinal and Organic Chemistry and Excellence Research Unit of Chemistry Applied to Biomedicine and the Environment, Faculty of Pharmacy, Campus Cartuja s/n, University of Granada, 18071 Granada, Spain
Victoria Cano-Cortés
Department of Medicinal and Organic Chemistry and Excellence Research Unit of Chemistry Applied to Biomedicine and the Environment, Faculty of Pharmacy, Campus Cartuja s/n, University of Granada, 18071 Granada, Spain
Olga Cruz-López
Department of Medicinal and Organic Chemistry and Excellence Research Unit of Chemistry Applied to Biomedicine and the Environment, Faculty of Pharmacy, Campus Cartuja s/n, University of Granada, 18071 Granada, Spain
Saúl Gonzalez-Resines
Department of Chemistry, University of Bath, Claverton Down, Bath BA2 7AX, UK
Carmen Domene
Department of Chemistry, University of Bath, Claverton Down, Bath BA2 7AX, UK
Ana Conejo-García
Department of Medicinal and Organic Chemistry and Excellence Research Unit of Chemistry Applied to Biomedicine and the Environment, Faculty of Pharmacy, Campus Cartuja s/n, University of Granada, 18071 Granada, Spain
Rosario M. Sánchez-Martín
Department of Medicinal and Organic Chemistry and Excellence Research Unit of Chemistry Applied to Biomedicine and the Environment, Faculty of Pharmacy, Campus Cartuja s/n, University of Granada, 18071 Granada, Spain
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.
