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...

Fuld beskrivelse

Bibliografiske detaljer
Main Authors: Alberto Martín-Asensio, Sergio Dávila, Jean Cacheux, Agnieszka Lindstaedt, Alicja Dziadosz, Darius Witt, Macarena Calero, Igor Balaz, Isabel Rodríguez
Format: Article
Sprog:English
Udgivet: Wiley-VCH 2023-06-01
Serier:Advanced NanoBiomed Research
Fag:
Online adgang:https://doi.org/10.1002/anbr.202200164
_version_ 1827932331107680256
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
format Article
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
work_keys_str_mv AT albertomartinasensio recapitulatingsolidstressontumoronachipfornanomedicinediffusivetransportprediction
AT sergiodavila recapitulatingsolidstressontumoronachipfornanomedicinediffusivetransportprediction
AT jeancacheux recapitulatingsolidstressontumoronachipfornanomedicinediffusivetransportprediction
AT agnieszkalindstaedt recapitulatingsolidstressontumoronachipfornanomedicinediffusivetransportprediction
AT alicjadziadosz recapitulatingsolidstressontumoronachipfornanomedicinediffusivetransportprediction
AT dariuswitt recapitulatingsolidstressontumoronachipfornanomedicinediffusivetransportprediction
AT macarenacalero recapitulatingsolidstressontumoronachipfornanomedicinediffusivetransportprediction
AT igorbalaz recapitulatingsolidstressontumoronachipfornanomedicinediffusivetransportprediction
AT isabelrodriguez recapitulatingsolidstressontumoronachipfornanomedicinediffusivetransportprediction