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

Research output: Contribution to journalArticlepeer-review

Abstract

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.
Original languageEnglish
Article number788
JournalPharmaceutics
Volume14
Issue number4
DOIs
Publication statusPublished - 4 Apr 2022

Keywords

  • anticancer therapy
  • cluster of differentiation 44
  • hyaluronic acid
  • molecular dynamics simulations
  • nanomedicine
  • selective release
  • tetrahydroisoquinoline

ASJC Scopus subject areas

  • Pharmaceutical Science

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