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

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dc.contributor.authorEspejo-Roman, Jose M
dc.contributor.authorRubio-Ruiz, Belen
dc.contributor.authorCano-Cortes, Victoria
dc.contributor.authorCruz-Lopez, Olga
dc.contributor.authorGonzalez-Resines, Saul
dc.contributor.authorDomene, Carmen
dc.contributor.authorConejo-Garcia, Ana
dc.contributor.authorSanchez-Martin, Rosario M
dc.contributor.funderConsejería de Economía, Conocimiento, Empresas y Universidad of the Junta de Andalucía
dc.contributor.funderResearch Results Transfer Office (OTRI) of the University of Granada
dc.contributor.funderHealth Institute Carlos III (ISCIII)
dc.date.accessioned2023-05-03T14:20:56Z
dc.date.available2023-05-03T14:20:56Z
dc.date.issued2022-04-01
dc.description.abstractHyaluronic 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.
dc.description.sponsorshipThis research was funded by the Consejería de Economía, Conocimiento, Empresas y Universidad of the Junta de Andalucía (grant number Excellence Research Project P18-RT-1679) and the Research Results Transfer Office (OTRI) of the University of Granada (grant number PR/17/006 project). This work was partially supported by grants from the Spanish Ministry of Economy and Competitiveness (MINECO), grant number PID2019.110987RB.I00; the Health Institute Carlos III (ISCIII), grant number DTS18/00121 the Junta de Andalucía-FEDER, Ministry of Economy, Knowledge, Companies, and University (FEDER 2018: ref. B-FQM-475-UGR18, PAIDI2020: ref. PT18-TP-4160); and the Andalusian Regional Government, grant number PAIDI-TC-PVT-PSETC-2.0. C.D. thanks HECBioSim, the UK High End Computing Consortium for Biomolecular Simulation (hecbiosim.ac.uk), which is supported by the EPSRC (EP/L000253/1) for awarding computing time in Jade, a UK Tier-2 resource. B.R.-R. gratefully acknowledges funding from the European Union’s Horizon 2020 Research and Innovation Program under Marie Sklodowska-Curie Grant Agreement no. 754446 and UGR Research and Knowledge Transfer Fund—Athenea3i. J.M.E.-R. thanks the Spanish Ministry of Education for PhD funding (scholarship FPU 16/02061). V.C.-C. thanks the Andalusian Regional Government for her postdoctoral fellowship (POSTDOC_21_00118).
dc.description.versionSi
dc.identifier.citationEspejo-Román JM, Rubio-Ruiz B, Cano-Cortés V, Cruz-López O, Gonzalez-Resines S, Domene C, et al. Selective Anticancer Therapy Based on a HA-CD44 Interaction Inhibitor Loaded on Polymeric Nanoparticles. Pharmaceutics. 2022 Apr 4;14(4):788.
dc.identifier.doi10.3390/pharmaceutics14040788
dc.identifier.issn1999-4923
dc.identifier.pmcPMC9032636
dc.identifier.pmid35456622
dc.identifier.pubmedURLhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9032636/pdf
dc.identifier.unpaywallURLhttps://www.mdpi.com/1999-4923/14/4/788/pdf?version=1649758834
dc.identifier.urihttp://hdl.handle.net/10668/21548
dc.issue.number4
dc.journal.titlePharmaceutics
dc.journal.titleabbreviationPharmaceutics
dc.language.isoen
dc.organizationCentro Pfizer-Universidad de Granada-Junta de Andalucía de Genómica e Investigación Oncológica-GENYO
dc.organizationInstituto de Investigación Biosanitaria de Granada (ibs.GRANADA)
dc.page.number20
dc.publisherMDPI AG
dc.pubmedtypeJournal Article
dc.relation.projectIDP18-RT-1679
dc.relation.projectIDPR/17/006
dc.relation.projectIDSpanish Ministry of Economy and Competitiveness (MINECO)
dc.relation.projectIDPID2019.110987RB.I00
dc.relation.projectIDDTS18/00121
dc.relation.publisherversionhttps://www.mdpi.com/resolver?pii=pharmaceutics14040788
dc.rightsAttribution 4.0 International
dc.rights.accessRightsopen access
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectanticancer therapy
dc.subjectcluster of differentiation 44
dc.subjecthyaluronic acid
dc.subjectmolecular dynamics simulations
dc.subjectnanomedicine
dc.subjectselective release
dc.subjecttetrahydroisoquinoline
dc.subject.decsMicroambiente tumoral
dc.subject.decsLiberación de fármacos
dc.subject.decsMovimiento celular
dc.subject.decsNeoplasias
dc.subject.decsNeovascularización patológica
dc.subject.decsProcesos neoplásicos
dc.subject.decsSitios de unión
dc.subject.decsSupervivencia celular
dc.subject.decsÁcido hialurónico
dc.subject.meshHyaluronic Acid
dc.subject.meshCell Movement
dc.subject.meshBinding Sites
dc.subject.meshNeovascularization, Pathologic
dc.subject.meshNeoplastic Processes
dc.subject.meshNeoplasms
dc.subject.meshTumor Microenvironment
dc.subject.meshDrug Liberation
dc.subject.meshCell Survival
dc.titleSelective Anticancer Therapy Based on a HA-CD44 Interaction Inhibitor Loaded on Polymeric Nanoparticles.
dc.typeresearch article
dc.type.hasVersionVoR
dc.volume.number14
dspace.entity.typePublication

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