A Two-Photon Microimaging-Microdevice System for Four-Dimensional Imaging of Local Drug Delivery in Tissues
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ijms-22-11752-v2.pdf
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3.73 MB
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Author(s)
Liu, Guigen
Valvo, Veronica
Ahn, Sebastian W.
Thompson, Devon
Deans, Kyle
Kang, Jeon Woong
Bhagavatula, Sharath
Dominas, Christine
Jonas, Oliver
Date Issued
October 29, 2021
Publisher
Multidisciplinary Digital Publishing Institute
Citation
International Journal of Molecular Sciences 22 (21): 11752 (2021)
Version
Final published version
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Laser Biomedical Research Center
Massachusetts Institute of Technology. Spectroscopy Laboratory
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DOI of Published Version
https://doi.org/10.3390/ijms222111752
