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

doi:10.3390/pharmaceutics14040788

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

Department of Chemistry

Research output: Contribution to journal › Article › peer-review

6 Citations (SciVal)

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 language	English
Article number	788
Journal	Pharmaceutics
Volume	14
Issue number	4
DOIs	https://doi.org/10.3390/pharmaceutics14040788
Publication status	Published - 4 Apr 2022

Bibliographical note

Funding Information:
This 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 Car-los 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).

Funding Information:
Funding: This 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).

Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

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

ASJC Scopus subject areas

Pharmaceutical Science

Access to Document

10.3390/pharmaceutics14040788Licence: CC BY

Cite this

@article{a087dce4d66541ebae4e7acde734f808,

title = "Selective Anticancer Therapy Based on a HA-CD44 Interaction Inhibitor Loaded on Polymeric Nanoparticles",

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.",

keywords = "anticancer therapy, cluster of differentiation 44, hyaluronic acid, molecular dynamics simulations, nanomedicine, selective release, tetrahydroisoquinoline",

author = "Espejo-rom{\'a}n, {Jos{\'e} M.} and Bel{\'e}n Rubio-Ruiz and Victoria Cano-Cort{\'e}s and Olga Cruz-L{\'o}pez and Sa{\'u}l Gonzalez-resines and Carmen Domene and Ana Conejo-Garc{\'i}a and S{\'a}nchez-Mart{\'i}n, {Rosario M.}",

note = "Funding Information: This research was funded by the Consejer{\'i}a de Econom{\'i}a, Conocimiento, Empresas y Universidad of the Junta de Andaluc{\'i}a (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 Car-los III (ISCIII), grant number DTS18/00121 the Junta de Andaluc{\'i}a-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{\textquoteright}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). Funding Information: Funding: This research was funded by the Consejer{\'i}a de Econom{\'i}a, Conocimiento, Empresas y Universidad of the Junta de Andaluc{\'i}a (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 Andaluc{\'i}a-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{\textquoteright}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). Publisher Copyright: {\textcopyright} 2022 by the authors. Licensee MDPI, Basel, Switzerland.",

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doi = "10.3390/pharmaceutics14040788",

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AU - Espejo-román, José M.

AU - Rubio-Ruiz, Belén

AU - Cano-Cortés, Victoria

AU - Cruz-López, Olga

AU - Gonzalez-resines, Saúl

AU - Domene, Carmen

AU - Conejo-García, Ana

AU - Sánchez-Martín, Rosario M.

N1 - Funding Information: This 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 Car-los 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). Funding Information: Funding: This 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). Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2022/4/4

Y1 - 2022/4/4

N2 - 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.

AB - 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.

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DO - 10.3390/pharmaceutics14040788

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VL - 14

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JF - Pharmaceutics

IS - 4

M1 - 788

ER -

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Confocal Laser Scanning Confocal Microscope (LSM)

Confocal Laser Scanning Microscope Zeiss LSM-880 with Airyscan and multiphoton laser

Electrospray Time-of-Flight Mass Spectrometer (Open-Access)

Cite this

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Equipment

Confocal Laser Scanning Confocal Microscope (LSM)

Confocal Laser Scanning Microscope Zeiss LSM-880 with Airyscan and multiphoton laser

Electrospray Time-of-Flight Mass Spectrometer (Open-Access)

Cite this