A Two-Photon Microimaging-Microdevice System for Four-Dimensional Imaging of Local Drug Delivery in Tissues

Advances in the intratumor measurement of drug responses have included a pioneering biomedical microdevice for high throughput drug screening in vivo, which was further advanced by integrating a graded-index lens based two-dimensional fluorescence micro-endoscope to monitor tissue responses in situ...

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Autores principales:	Guigen Liu, Veronica Valvo, Sebastian W. Ahn, Devon Thompson, Kyle Deans, Jeon Woong Kang, Sharath Bhagavatula, Christine Dominas, Oliver Jonas
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	biomedical microdevice two-photon micro-endoscopy optical sectioning local drug delivery tumors in vivo testing Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/a79757821daf4e97b97d09630f3a30f9
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spelling	oai:doaj.org-article:a79757821daf4e97b97d09630f3a30f92021-11-11T17:12:24ZA Two-Photon Microimaging-Microdevice System for Four-Dimensional Imaging of Local Drug Delivery in Tissues10.3390/ijms2221117521422-00671661-6596https://doaj.org/article/a79757821daf4e97b97d09630f3a30f92021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11752https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Advances in the intratumor measurement of drug responses have included a pioneering biomedical microdevice for high throughput drug screening in vivo, which was further advanced by integrating a graded-index lens based two-dimensional fluorescence micro-endoscope to monitor tissue responses in situ across time. While the previous system provided a bulk measurement of both drug delivery and tissue response from a given region of the tumor, it was incapable of visualizing drug distribution and tissue responses in a three-dimensional (3D) way, thus missing the critical relationship between drug concentration and effect. Here we demonstrate a next-generation system that couples multiplexed intratumor drug release with continuous 3D spatial imaging of the tumor microenvironment via the integration of a miniaturized two-photon micro-endoscope. This enables optical sectioning within the live tissue microenvironment to effectively profile the entire tumor region adjacent to the microdevice across time. Using this novel microimaging-microdevice (MI-MD) system, we successfully demonstrated the four-dimensional imaging (3 spatial dimensions plus time) of local drug delivery in tissue phantom and tumors. Future studies include the use of the MI-MD system for monitoring of localized intra-tissue drug release and concurrent measurement of tissue responses in live organisms, with applications to study drug resistance due to nonuniform drug distribution in tumors, or immune cell responses to anti-cancer agents.Guigen LiuVeronica ValvoSebastian W. AhnDevon ThompsonKyle DeansJeon Woong KangSharath BhagavatulaChristine DominasOliver JonasMDPI AGarticlebiomedical microdevicetwo-photon micro-endoscopyoptical sectioninglocal drug deliverytumorsin vivo testingBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11752, p 11752 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	biomedical microdevice two-photon micro-endoscopy optical sectioning local drug delivery tumors in vivo testing Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	biomedical microdevice two-photon micro-endoscopy optical sectioning local drug delivery tumors in vivo testing Biology (General) QH301-705.5 Chemistry QD1-999 Guigen Liu Veronica Valvo Sebastian W. Ahn Devon Thompson Kyle Deans Jeon Woong Kang Sharath Bhagavatula Christine Dominas Oliver Jonas A Two-Photon Microimaging-Microdevice System for Four-Dimensional Imaging of Local Drug Delivery in Tissues
description	Advances in the intratumor measurement of drug responses have included a pioneering biomedical microdevice for high throughput drug screening in vivo, which was further advanced by integrating a graded-index lens based two-dimensional fluorescence micro-endoscope to monitor tissue responses in situ across time. While the previous system provided a bulk measurement of both drug delivery and tissue response from a given region of the tumor, it was incapable of visualizing drug distribution and tissue responses in a three-dimensional (3D) way, thus missing the critical relationship between drug concentration and effect. Here we demonstrate a next-generation system that couples multiplexed intratumor drug release with continuous 3D spatial imaging of the tumor microenvironment via the integration of a miniaturized two-photon micro-endoscope. This enables optical sectioning within the live tissue microenvironment to effectively profile the entire tumor region adjacent to the microdevice across time. Using this novel microimaging-microdevice (MI-MD) system, we successfully demonstrated the four-dimensional imaging (3 spatial dimensions plus time) of local drug delivery in tissue phantom and tumors. Future studies include the use of the MI-MD system for monitoring of localized intra-tissue drug release and concurrent measurement of tissue responses in live organisms, with applications to study drug resistance due to nonuniform drug distribution in tumors, or immune cell responses to anti-cancer agents.
format	article
author	Guigen Liu Veronica Valvo Sebastian W. Ahn Devon Thompson Kyle Deans Jeon Woong Kang Sharath Bhagavatula Christine Dominas Oliver Jonas
author_facet	Guigen Liu Veronica Valvo Sebastian W. Ahn Devon Thompson Kyle Deans Jeon Woong Kang Sharath Bhagavatula Christine Dominas Oliver Jonas
author_sort	Guigen Liu
title	A Two-Photon Microimaging-Microdevice System for Four-Dimensional Imaging of Local Drug Delivery in Tissues
title_short	A Two-Photon Microimaging-Microdevice System for Four-Dimensional Imaging of Local Drug Delivery in Tissues
title_full	A Two-Photon Microimaging-Microdevice System for Four-Dimensional Imaging of Local Drug Delivery in Tissues
title_fullStr	A Two-Photon Microimaging-Microdevice System for Four-Dimensional Imaging of Local Drug Delivery in Tissues
title_full_unstemmed	A Two-Photon Microimaging-Microdevice System for Four-Dimensional Imaging of Local Drug Delivery in Tissues
title_sort	two-photon microimaging-microdevice system for four-dimensional imaging of local drug delivery in tissues
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/a79757821daf4e97b97d09630f3a30f9
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A Two-Photon Microimaging-Microdevice System for Four-Dimensional Imaging of Local Drug Delivery in Tissues

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