YAP Signaling Regulates the Cellular Uptake and Therapeutic Effect of Nanoparticles

Abstract Interactions between living cells and nanoparticles are extensively studied to enhance the delivery of therapeutics. Nanoparticles size, shape, stiffness, and surface charge are regarded as the main features able to control the fate of cell‐nanoparticle interactions. However, the clinical t...

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Main Authors: Marco Cassani, Soraia Fernandes, Jorge Oliver‐De La Cruz, Helena Durikova, Jan Vrbsky, Marek Patočka, Veronika Hegrova, Simon Klimovic, Jan Pribyl, Doriana Debellis, Petr Skladal, Francesca Cavalieri, Frank Caruso, Giancarlo Forte
Format: Article
Language:English
Published: Wiley 2024-01-01
Series:Advanced Science
Subjects:
Online Access:https://doi.org/10.1002/advs.202302965
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author Marco Cassani
Soraia Fernandes
Jorge Oliver‐De La Cruz
Helena Durikova
Jan Vrbsky
Marek Patočka
Veronika Hegrova
Simon Klimovic
Jan Pribyl
Doriana Debellis
Petr Skladal
Francesca Cavalieri
Frank Caruso
Giancarlo Forte
author_facet Marco Cassani
Soraia Fernandes
Jorge Oliver‐De La Cruz
Helena Durikova
Jan Vrbsky
Marek Patočka
Veronika Hegrova
Simon Klimovic
Jan Pribyl
Doriana Debellis
Petr Skladal
Francesca Cavalieri
Frank Caruso
Giancarlo Forte
author_sort Marco Cassani
collection DOAJ
description Abstract Interactions between living cells and nanoparticles are extensively studied to enhance the delivery of therapeutics. Nanoparticles size, shape, stiffness, and surface charge are regarded as the main features able to control the fate of cell‐nanoparticle interactions. However, the clinical translation of nanotherapies has so far been limited, and there is a need to better understand the biology of cell‐nanoparticle interactions. This study investigates the role of cellular mechanosensitive components in cell‐nanoparticle interactions. It is demonstrated that the genetic and pharmacologic inhibition of yes‐associated protein (YAP), a key component of cancer cell mechanosensing apparatus and Hippo pathway effector, improves nanoparticle internalization in triple‐negative breast cancer cells regardless of nanoparticle properties or substrate characteristics. This process occurs through YAP‐dependent regulation of endocytic pathways, cell mechanics, and membrane organization. Hence, the study proposes targeting YAP may sensitize triple‐negative breast cancer cells to chemotherapy and increase the selectivity of nanotherapy.
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spelling doaj.art-c4120ba3908f4da5bb68047683a627532024-01-13T04:23:06ZengWileyAdvanced Science2198-38442024-01-01112n/an/a10.1002/advs.202302965YAP Signaling Regulates the Cellular Uptake and Therapeutic Effect of NanoparticlesMarco Cassani0Soraia Fernandes1Jorge Oliver‐De La Cruz2Helena Durikova3Jan Vrbsky4Marek Patočka5Veronika Hegrova6Simon Klimovic7Jan Pribyl8Doriana Debellis9Petr Skladal10Francesca Cavalieri11Frank Caruso12Giancarlo Forte13International Clinical Research Center St. Anne's University Hospital Brno 60200 Czech RepublicInternational Clinical Research Center St. Anne's University Hospital Brno 60200 Czech RepublicInternational Clinical Research Center St. Anne's University Hospital Brno 60200 Czech RepublicInternational Clinical Research Center St. Anne's University Hospital Brno 60200 Czech RepublicInternational Clinical Research Center St. Anne's University Hospital Brno 60200 Czech RepublicNenoVision Purkynova 649/127 Brno 61200 Czech RepublicNenoVision Purkynova 649/127 Brno 61200 Czech RepublicDepartment of Bioanalytical Instrumentation CEITEC Masaryk University Brno 60200 Czech RepublicDepartment of Bioanalytical Instrumentation CEITEC Masaryk University Brno 60200 Czech RepublicElectron Microscopy Facility Fondazione Istituto Italiano Di Tecnologia Via Morego 30 Genoa 16163 ItalyDepartment of Bioanalytical Instrumentation CEITEC Masaryk University Brno 60200 Czech RepublicDepartment of Chemical Engineering The University of Melbourne Parkville Victoria 3010 AustraliaDepartment of Chemical Engineering The University of Melbourne Parkville Victoria 3010 AustraliaInternational Clinical Research Center St. Anne's University Hospital Brno 60200 Czech RepublicAbstract Interactions between living cells and nanoparticles are extensively studied to enhance the delivery of therapeutics. Nanoparticles size, shape, stiffness, and surface charge are regarded as the main features able to control the fate of cell‐nanoparticle interactions. However, the clinical translation of nanotherapies has so far been limited, and there is a need to better understand the biology of cell‐nanoparticle interactions. This study investigates the role of cellular mechanosensitive components in cell‐nanoparticle interactions. It is demonstrated that the genetic and pharmacologic inhibition of yes‐associated protein (YAP), a key component of cancer cell mechanosensing apparatus and Hippo pathway effector, improves nanoparticle internalization in triple‐negative breast cancer cells regardless of nanoparticle properties or substrate characteristics. This process occurs through YAP‐dependent regulation of endocytic pathways, cell mechanics, and membrane organization. Hence, the study proposes targeting YAP may sensitize triple‐negative breast cancer cells to chemotherapy and increase the selectivity of nanotherapy.https://doi.org/10.1002/advs.202302965bio‐nano interactionscancer treatmentmechanobiologynanoparticlesYAP‐signaling
spellingShingle Marco Cassani
Soraia Fernandes
Jorge Oliver‐De La Cruz
Helena Durikova
Jan Vrbsky
Marek Patočka
Veronika Hegrova
Simon Klimovic
Jan Pribyl
Doriana Debellis
Petr Skladal
Francesca Cavalieri
Frank Caruso
Giancarlo Forte
YAP Signaling Regulates the Cellular Uptake and Therapeutic Effect of Nanoparticles
Advanced Science
bio‐nano interactions
cancer treatment
mechanobiology
nanoparticles
YAP‐signaling
title YAP Signaling Regulates the Cellular Uptake and Therapeutic Effect of Nanoparticles
title_full YAP Signaling Regulates the Cellular Uptake and Therapeutic Effect of Nanoparticles
title_fullStr YAP Signaling Regulates the Cellular Uptake and Therapeutic Effect of Nanoparticles
title_full_unstemmed YAP Signaling Regulates the Cellular Uptake and Therapeutic Effect of Nanoparticles
title_short YAP Signaling Regulates the Cellular Uptake and Therapeutic Effect of Nanoparticles
title_sort yap signaling regulates the cellular uptake and therapeutic effect of nanoparticles
topic bio‐nano interactions
cancer treatment
mechanobiology
nanoparticles
YAP‐signaling
url https://doi.org/10.1002/advs.202302965
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