Selective Anticancer Therapy Based on a HA-CD44 Interaction Inhibitor Loaded on Polymeric Nanoparticles
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AuthorEspejo Román, José Manuel; Rubio Ruiz, Belén; Cano Cortes, María Victoria; Cruz López, Olga María; Conejo García, Ana; Sánchez Martín, Rosario María
NanomedicineSelective releaseAnticancer therapyHyaluronic acidCluster of differentiation 44TetrahydroisoquinolineMolecular dynamics simulations
Espejo-Román, J.M... [et al.]. Selective Anticancer Therapy Based on a HA-CD44 Interaction Inhibitor Loaded on Polymeric Nanoparticles. Pharmaceutics 2022, 14, 788. [https://doi.org/10.3390/pharmaceutics14040788]
SponsorshipJunta de Andalucia P18-RT-1679; Research Results Transfer Office (OTRI) of the University of Granada PR/17/006; Spanish Government PID2019.110987RB.I00; Health Institute Carlos III (ISCIII) DTS18/00121; Junta de Andalucia-FEDER, Ministry of Economy, Knowledge, Companies, and University (FEDER) B-FQM-475-UGR18 PT18-TP-4160; Andalusian Regional Government POSTDOC_21_00118; UK Research & Innovation (UKRI); Engineering & Physical Sciences Research Council (EPSRC) EP/L000253/1; European Union's Horizon 2020 Research and Innovation Program under Marie Sklodowska-Curie Grant 754446; UGR Research and Knowledge Transfer Fund-Athenea3i; Spanish Government FPU 16/02061
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 HACD44 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.