Measuring Nanoparticle Penetration Through Bio-Mimetic Gels

Scott C McCormick,1,* Namid Stillman,1,* Matthew Hockley,1 Adam W Perriman,2 Sabine Hauert1 1Engineering Mathematics, University of Bristol, Bristol, BS8 1UB, UK; 2Biomedical Sciences, University of Bristol, Bristol, BS8 1TD, UK*These authors contributed equally to this workCorrespondence: Sabine Ha...

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Autores principales:	McCormick SC, Stillman N, Hockley M, Perriman AW, Hauert S
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	nanomedicine microfluidics transport barriers tissue penetration image processing fast-prototyping Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/332caf51a2a3425faf27b6f848bdd7b3
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spelling	oai:doaj.org-article:332caf51a2a3425faf27b6f848bdd7b32021-12-02T14:25:40ZMeasuring Nanoparticle Penetration Through Bio-Mimetic Gels1178-2013https://doaj.org/article/332caf51a2a3425faf27b6f848bdd7b32021-03-01T00:00:00Zhttps://www.dovepress.com/measuring-nanoparticle-penetration-through-bio-mimetic-gels-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Scott C McCormick,1,* Namid Stillman,1,* Matthew Hockley,1 Adam W Perriman,2 Sabine Hauert1 1Engineering Mathematics, University of Bristol, Bristol, BS8 1UB, UK; 2Biomedical Sciences, University of Bristol, Bristol, BS8 1TD, UK*These authors contributed equally to this workCorrespondence: Sabine HauertEngineering Mathematics, University of Bristol, Bristol, BS8 1UB, UKEmail sabine.hauert@bristol.ac.ukBackground: In cancer nanomedicine, drugs are transported by nanocarriers through a biological system to produce a therapeutic effect. The efficacy of the treatment is affected by the ability of the nanocarriers to overcome biological transport barriers to reach their target. In this work, we focus on the process of nanocarrier penetration through tumour tissue after extravasation. Visualising the dynamics of nanocarriers in tissue is difficult in vivo, and in vitro assays often do not capture the spatial and physical constraints relevant to model tissue penetration.Methods: We propose a new simple, low-cost method to observe the transport dynamics of nanoparticles through a tissue-mimetic microfluidic chip. After loading a chip with triplicate conditions of gel type and loading with microparticles, microscopic analysis allows for tracking of fluorescent nanoparticles as they move through hydrogels (Matrigel and Collagen I) with and without cell-sized microparticles. A bespoke image-processing codebase written in MATLAB allows for statistical analysis of this tracking, and time-dependent dynamics can be determined.Results: To demonstrate the method, we show size-dependence of transport mechanics can be observed, with diffusion of fluorescein dye throughout the channel in 8 h, while 20 nm carboxylate FluoSphere diffusion was hindered through both Collagen I and Matrigel™. Statistical measurements of the results are generated through the software package and show the significance of both size and presence of microparticles on penetration depth.Conclusion: This provides an easy-to-understand output for the end user to measure nanoparticle tissue penetration, enabling the first steps towards future automated experimentation of transport dynamics for rational nanocarrier design.Keywords: nanomedicine, microfluidics, transport barriers, tissue penetration, image processing, fast-prototypingMcCormick SCStillman NHockley MPerriman AWHauert SDove Medical Pressarticlenanomedicinemicrofluidicstransport barrierstissue penetrationimage processingfast-prototypingMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 16, Pp 2585-2595 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	nanomedicine microfluidics transport barriers tissue penetration image processing fast-prototyping Medicine (General) R5-920
spellingShingle	nanomedicine microfluidics transport barriers tissue penetration image processing fast-prototyping Medicine (General) R5-920 McCormick SC Stillman N Hockley M Perriman AW Hauert S Measuring Nanoparticle Penetration Through Bio-Mimetic Gels
description	Scott C McCormick,1,* Namid Stillman,1,* Matthew Hockley,1 Adam W Perriman,2 Sabine Hauert1 1Engineering Mathematics, University of Bristol, Bristol, BS8 1UB, UK; 2Biomedical Sciences, University of Bristol, Bristol, BS8 1TD, UK*These authors contributed equally to this workCorrespondence: Sabine HauertEngineering Mathematics, University of Bristol, Bristol, BS8 1UB, UKEmail sabine.hauert@bristol.ac.ukBackground: In cancer nanomedicine, drugs are transported by nanocarriers through a biological system to produce a therapeutic effect. The efficacy of the treatment is affected by the ability of the nanocarriers to overcome biological transport barriers to reach their target. In this work, we focus on the process of nanocarrier penetration through tumour tissue after extravasation. Visualising the dynamics of nanocarriers in tissue is difficult in vivo, and in vitro assays often do not capture the spatial and physical constraints relevant to model tissue penetration.Methods: We propose a new simple, low-cost method to observe the transport dynamics of nanoparticles through a tissue-mimetic microfluidic chip. After loading a chip with triplicate conditions of gel type and loading with microparticles, microscopic analysis allows for tracking of fluorescent nanoparticles as they move through hydrogels (Matrigel and Collagen I) with and without cell-sized microparticles. A bespoke image-processing codebase written in MATLAB allows for statistical analysis of this tracking, and time-dependent dynamics can be determined.Results: To demonstrate the method, we show size-dependence of transport mechanics can be observed, with diffusion of fluorescein dye throughout the channel in 8 h, while 20 nm carboxylate FluoSphere diffusion was hindered through both Collagen I and Matrigel™. Statistical measurements of the results are generated through the software package and show the significance of both size and presence of microparticles on penetration depth.Conclusion: This provides an easy-to-understand output for the end user to measure nanoparticle tissue penetration, enabling the first steps towards future automated experimentation of transport dynamics for rational nanocarrier design.Keywords: nanomedicine, microfluidics, transport barriers, tissue penetration, image processing, fast-prototyping
format	article
author	McCormick SC Stillman N Hockley M Perriman AW Hauert S
author_facet	McCormick SC Stillman N Hockley M Perriman AW Hauert S
author_sort	McCormick SC
title	Measuring Nanoparticle Penetration Through Bio-Mimetic Gels
title_short	Measuring Nanoparticle Penetration Through Bio-Mimetic Gels
title_full	Measuring Nanoparticle Penetration Through Bio-Mimetic Gels
title_fullStr	Measuring Nanoparticle Penetration Through Bio-Mimetic Gels
title_full_unstemmed	Measuring Nanoparticle Penetration Through Bio-Mimetic Gels
title_sort	measuring nanoparticle penetration through bio-mimetic gels
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/332caf51a2a3425faf27b6f848bdd7b3
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Measuring Nanoparticle Penetration Through Bio-Mimetic Gels

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