Recapitulating Solid Stress on Tumor on a Chip for Nanomedicine Diffusive Transport Prediction
The characteristic mechanical forces at play within tumors include the abnormal solid and fluid stresses. These, together with the increased extracellular matrix (ECM) stiffness, are the major transport barriers affecting the nanomedicine delivery to solid tumors. Due to the elevated pressure within...
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Format: | Article |
Sprog: | English |
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Wiley-VCH
2023-06-01
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Serier: | Advanced NanoBiomed Research |
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Online adgang: | https://doi.org/10.1002/anbr.202200164 |
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author | Alberto Martín-Asensio Sergio Dávila Jean Cacheux Agnieszka Lindstaedt Alicja Dziadosz Darius Witt Macarena Calero Igor Balaz Isabel Rodríguez |
author_facet | Alberto Martín-Asensio Sergio Dávila Jean Cacheux Agnieszka Lindstaedt Alicja Dziadosz Darius Witt Macarena Calero Igor Balaz Isabel Rodríguez |
author_sort | Alberto Martín-Asensio |
collection | DOAJ |
description | The characteristic mechanical forces at play within tumors include the abnormal solid and fluid stresses. These, together with the increased extracellular matrix (ECM) stiffness, are the major transport barriers affecting the nanomedicine delivery to solid tumors. Due to the elevated pressure within the tumor microenvironment, the transport of nanomedicines through the interstitial space is limited to diffusion. While this particular scenario is central for nanomedicine delivery to solid tumors, it has not been modeled in vitro before. To this end, herein, a tumor‐on‐a‐chip microfluidic device is developed that is capable of recapitulating the solid stress scenario in tumors. This is achieved by integrating a pneumatic actuation to apply compression to the enclosed hydrogel ECM filling medium. Transport studies of model nanoparticles (NPs) across this medium are performed to determine their diffusion. For these NPs, it is demonstrated that their transport is drastically reduced by 65% due to the compression of the ECM gel matrix, reducing its pore size, with only an applied pressure of ≈4 Pa. The results obtained show that the actuated tumor‐on‐a‐chip device can be used to evaluate the diffusive penetration capability of nanomedicines within a mechanical‐constrained microenvironment such that of tumors. |
first_indexed | 2024-03-13T07:07:05Z |
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id | doaj.art-f702c5bbd5224523bfeb511b949a6f4d |
institution | Directory Open Access Journal |
issn | 2699-9307 |
language | English |
last_indexed | 2024-03-13T07:07:05Z |
publishDate | 2023-06-01 |
publisher | Wiley-VCH |
record_format | Article |
series | Advanced NanoBiomed Research |
spelling | doaj.art-f702c5bbd5224523bfeb511b949a6f4d2023-06-06T08:46:35ZengWiley-VCHAdvanced NanoBiomed Research2699-93072023-06-0136n/an/a10.1002/anbr.202200164Recapitulating Solid Stress on Tumor on a Chip for Nanomedicine Diffusive Transport PredictionAlberto Martín-Asensio0Sergio Dávila1Jean Cacheux2Agnieszka Lindstaedt3Alicja Dziadosz4Darius Witt5Macarena Calero6Igor Balaz7Isabel Rodríguez8IMDEA Nanoscience Institute 28049 Madrid SpainIMDEA Nanoscience Institute 28049 Madrid SpainIMDEA Nanoscience Institute 28049 Madrid SpainProChimia Surfaces Sp. z o.o. 81-451 Gdynia PolandProChimia Surfaces Sp. z o.o. 81-451 Gdynia PolandProChimia Surfaces Sp. z o.o. 81-451 Gdynia PolandDepartment of Physical Chemistry Complutense University of Madrid 28040 Madrid SpainLaboratory for Meteorology, Physics, and Biophysics Faculty of Agriculture University of Novi Sad 21000 Novi Sad SerbiaIMDEA Nanoscience Institute 28049 Madrid SpainThe characteristic mechanical forces at play within tumors include the abnormal solid and fluid stresses. These, together with the increased extracellular matrix (ECM) stiffness, are the major transport barriers affecting the nanomedicine delivery to solid tumors. Due to the elevated pressure within the tumor microenvironment, the transport of nanomedicines through the interstitial space is limited to diffusion. While this particular scenario is central for nanomedicine delivery to solid tumors, it has not been modeled in vitro before. To this end, herein, a tumor‐on‐a‐chip microfluidic device is developed that is capable of recapitulating the solid stress scenario in tumors. This is achieved by integrating a pneumatic actuation to apply compression to the enclosed hydrogel ECM filling medium. Transport studies of model nanoparticles (NPs) across this medium are performed to determine their diffusion. For these NPs, it is demonstrated that their transport is drastically reduced by 65% due to the compression of the ECM gel matrix, reducing its pore size, with only an applied pressure of ≈4 Pa. The results obtained show that the actuated tumor‐on‐a‐chip device can be used to evaluate the diffusive penetration capability of nanomedicines within a mechanical‐constrained microenvironment such that of tumors.https://doi.org/10.1002/anbr.202200164microfluidicsnanomedicineorgan-on-a-chipsolid tumorstumor-on-a-chip |
spellingShingle | Alberto Martín-Asensio Sergio Dávila Jean Cacheux Agnieszka Lindstaedt Alicja Dziadosz Darius Witt Macarena Calero Igor Balaz Isabel Rodríguez Recapitulating Solid Stress on Tumor on a Chip for Nanomedicine Diffusive Transport Prediction Advanced NanoBiomed Research microfluidics nanomedicine organ-on-a-chip solid tumors tumor-on-a-chip |
title | Recapitulating Solid Stress on Tumor on a Chip for Nanomedicine Diffusive Transport Prediction |
title_full | Recapitulating Solid Stress on Tumor on a Chip for Nanomedicine Diffusive Transport Prediction |
title_fullStr | Recapitulating Solid Stress on Tumor on a Chip for Nanomedicine Diffusive Transport Prediction |
title_full_unstemmed | Recapitulating Solid Stress on Tumor on a Chip for Nanomedicine Diffusive Transport Prediction |
title_short | Recapitulating Solid Stress on Tumor on a Chip for Nanomedicine Diffusive Transport Prediction |
title_sort | recapitulating solid stress on tumor on a chip for nanomedicine diffusive transport prediction |
topic | microfluidics nanomedicine organ-on-a-chip solid tumors tumor-on-a-chip |
url | https://doi.org/10.1002/anbr.202200164 |
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