Regulation of Cell-Nanoparticle Interactions through Mechanobiology

Marco Cassani; Francesco Niro; Soraia Fernandes; Daniel Pereira-Sousa; Sofia Faes Morazzo; Helena Durikova; Tianzheng Wang; Lara González-Cabaleiro; Jan Vrbsky; Jorge Oliver-De La Cruz; Simon Klimovic; Jan Pribyl; Tomas Loja; Petr Skladal; Frank Caruso; Giancarlo Forte

doi:10.1021/acs.nanolett.4c04290

Regulation of Cell-Nanoparticle Interactions through Mechanobiology

Marco Cassani, Francesco Niro, Soraia Fernandes, Daniel Pereira-Sousa, Sofia Faes Morazzo, Helena Durikova, Tianzheng Wang, Lara González-Cabaleiro, Jan Vrbsky, Jorge Oliver-De La Cruz, Simon Klimovic, Jan Pribyl, Tomas Loja, Petr Skladal, Frank Caruso, Giancarlo Forte

SCMMS Denmark Hill

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

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Abstract

Bio-nano interactions have been extensively explored in nanomedicine to develop selective delivery strategies and reduce systemic toxicity. To enhance the delivery of nanocarriers to cancer cells and improve the therapeutic efficiency, different nanomaterials have been developed. However, the limited clinical translation of nanoparticle-based therapies, largely due to issues associated with poor targeting, requires a deeper understanding of the biological phenomena underlying cell-nanoparticle interactions. In this context, we investigate the molecular and cellular mechanobiology parameters that control such interactions. We demonstrate that the pharmacological inhibition or the genetic ablation of the key mechanosensitive component of the Hippo pathway, i.e., yes-associated protein, enhances nanoparticle internalization by 1.5-fold. Importantly, this phenomenon occurs independently of nanoparticle properties, such as size, or cell properties such as surface area and stiffness. Our study reveals that the internalization of nanoparticles in target cells can be controlled by modulating cell mechanosensing pathways, potentially enhancing nanotherapy specificity.

Original language	English
Pages (from-to)	2600-2609
Number of pages	10
Journal	Nano Letters
Volume	25
Issue number	7
Early online date	8 Jan 2025
DOIs	https://doi.org/10.1021/acs.nanolett.4c04290
Publication status	Published - 19 Feb 2025

Keywords

Humans
Nanoparticles/chemistry
YAP-Signaling Proteins
Mechanotransduction, Cellular/drug effects
Nanomedicine
Adaptor Proteins, Signal Transducing/metabolism
Hippo Signaling Pathway
Cell Line, Tumor
Animals

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Regulation of Cell_CASSANI_Publishedonline8January2025_GOLD VoR (CC-BY)Final published version, 9.32 MBLicence: CC BY

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Cassani, M., Niro, F., Fernandes, S., Pereira-Sousa, D., Faes Morazzo, S., Durikova, H., Wang, T., González-Cabaleiro, L., Vrbsky, J., Oliver-De La Cruz, J., Klimovic, S., Pribyl, J., Loja, T., Skladal, P., Caruso, F., & Forte, G. (2025). Regulation of Cell-Nanoparticle Interactions through Mechanobiology. Nano Letters, 25(7), 2600-2609. https://doi.org/10.1021/acs.nanolett.4c04290

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title = "Regulation of Cell-Nanoparticle Interactions through Mechanobiology",

abstract = "Bio-nano interactions have been extensively explored in nanomedicine to develop selective delivery strategies and reduce systemic toxicity. To enhance the delivery of nanocarriers to cancer cells and improve the therapeutic efficiency, different nanomaterials have been developed. However, the limited clinical translation of nanoparticle-based therapies, largely due to issues associated with poor targeting, requires a deeper understanding of the biological phenomena underlying cell-nanoparticle interactions. In this context, we investigate the molecular and cellular mechanobiology parameters that control such interactions. We demonstrate that the pharmacological inhibition or the genetic ablation of the key mechanosensitive component of the Hippo pathway, i.e., yes-associated protein, enhances nanoparticle internalization by 1.5-fold. Importantly, this phenomenon occurs independently of nanoparticle properties, such as size, or cell properties such as surface area and stiffness. Our study reveals that the internalization of nanoparticles in target cells can be controlled by modulating cell mechanosensing pathways, potentially enhancing nanotherapy specificity.",

keywords = "Humans, Nanoparticles/chemistry, YAP-Signaling Proteins, Mechanotransduction, Cellular/drug effects, Nanomedicine, Adaptor Proteins, Signal Transducing/metabolism, Hippo Signaling Pathway, Cell Line, Tumor, Animals",

author = "Marco Cassani and Francesco Niro and Soraia Fernandes and Daniel Pereira-Sousa and {Faes Morazzo}, Sofia and Helena Durikova and Tianzheng Wang and Lara Gonz{\'a}lez-Cabaleiro and Jan Vrbsky and {Oliver-De La Cruz}, Jorge and Simon Klimovic and Jan Pribyl and Tomas Loja and Petr Skladal and Frank Caruso and Giancarlo Forte",

note = "Publisher Copyright: {\textcopyright} 2025 The Authors. Published by American Chemical Society.",

year = "2025",

month = feb,

day = "19",

doi = "10.1021/acs.nanolett.4c04290",

language = "English",

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Cassani, M, Niro, F, Fernandes, S, Pereira-Sousa, D, Faes Morazzo, S, Durikova, H, Wang, T, González-Cabaleiro, L, Vrbsky, J, Oliver-De La Cruz, J, Klimovic, S, Pribyl, J, Loja, T, Skladal, P, Caruso, F & Forte, G 2025, 'Regulation of Cell-Nanoparticle Interactions through Mechanobiology', Nano Letters, vol. 25, no. 7, pp. 2600-2609. https://doi.org/10.1021/acs.nanolett.4c04290

TY - JOUR

T1 - Regulation of Cell-Nanoparticle Interactions through Mechanobiology

AU - Cassani, Marco

AU - Niro, Francesco

AU - Fernandes, Soraia

AU - Pereira-Sousa, Daniel

AU - Faes Morazzo, Sofia

AU - Durikova, Helena

AU - Wang, Tianzheng

AU - González-Cabaleiro, Lara

AU - Vrbsky, Jan

AU - Oliver-De La Cruz, Jorge

AU - Klimovic, Simon

AU - Pribyl, Jan

AU - Loja, Tomas

AU - Skladal, Petr

AU - Caruso, Frank

AU - Forte, Giancarlo

PY - 2025/2/19

Y1 - 2025/2/19

N2 - Bio-nano interactions have been extensively explored in nanomedicine to develop selective delivery strategies and reduce systemic toxicity. To enhance the delivery of nanocarriers to cancer cells and improve the therapeutic efficiency, different nanomaterials have been developed. However, the limited clinical translation of nanoparticle-based therapies, largely due to issues associated with poor targeting, requires a deeper understanding of the biological phenomena underlying cell-nanoparticle interactions. In this context, we investigate the molecular and cellular mechanobiology parameters that control such interactions. We demonstrate that the pharmacological inhibition or the genetic ablation of the key mechanosensitive component of the Hippo pathway, i.e., yes-associated protein, enhances nanoparticle internalization by 1.5-fold. Importantly, this phenomenon occurs independently of nanoparticle properties, such as size, or cell properties such as surface area and stiffness. Our study reveals that the internalization of nanoparticles in target cells can be controlled by modulating cell mechanosensing pathways, potentially enhancing nanotherapy specificity.

AB - Bio-nano interactions have been extensively explored in nanomedicine to develop selective delivery strategies and reduce systemic toxicity. To enhance the delivery of nanocarriers to cancer cells and improve the therapeutic efficiency, different nanomaterials have been developed. However, the limited clinical translation of nanoparticle-based therapies, largely due to issues associated with poor targeting, requires a deeper understanding of the biological phenomena underlying cell-nanoparticle interactions. In this context, we investigate the molecular and cellular mechanobiology parameters that control such interactions. We demonstrate that the pharmacological inhibition or the genetic ablation of the key mechanosensitive component of the Hippo pathway, i.e., yes-associated protein, enhances nanoparticle internalization by 1.5-fold. Importantly, this phenomenon occurs independently of nanoparticle properties, such as size, or cell properties such as surface area and stiffness. Our study reveals that the internalization of nanoparticles in target cells can be controlled by modulating cell mechanosensing pathways, potentially enhancing nanotherapy specificity.

KW - Humans

KW - Nanoparticles/chemistry

KW - YAP-Signaling Proteins

KW - Mechanotransduction, Cellular/drug effects

KW - Nanomedicine

KW - Adaptor Proteins, Signal Transducing/metabolism

KW - Hippo Signaling Pathway

KW - Cell Line, Tumor

KW - Animals

UR - http://www.scopus.com/inward/record.url?scp=85214674702&partnerID=8YFLogxK

U2 - 10.1021/acs.nanolett.4c04290

DO - 10.1021/acs.nanolett.4c04290

M3 - Article

C2 - 39772635

AN - SCOPUS:85214674702

SN - 1530-6984

VL - 25

SP - 2600

EP - 2609

JO - Nano Letters

JF - Nano Letters

IS - 7

ER -

Regulation of Cell-Nanoparticle Interactions through Mechanobiology

Abstract

Keywords

UN SDGs

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