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Article

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

by
Guigen Liu
1,
Veronica Valvo
1,
Sebastian W. Ahn
1,
Devon Thompson
1,
Kyle Deans
1,
Jeon Woong Kang
2,
Sharath Bhagavatula
1,
Christine Dominas
1 and
Oliver Jonas
1,*
1
Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, 221 Longwood Ave, Boston, MA 02115, USA
2
Laser Biomedical Research Center, G. R. Harrison Spectroscopy Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2021, 22(21), 11752; https://doi.org/10.3390/ijms222111752
Submission received: 13 October 2021 / Revised: 28 October 2021 / Accepted: 28 October 2021 / Published: 29 October 2021
(This article belongs to the Special Issue Challenges, Opportunities, and Innovation in Local Drug Delivery)
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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.
Keywords: biomedical microdevice; two-photon micro-endoscopy; optical sectioning; local drug delivery; tumors; in vivo testing biomedical microdevice; two-photon micro-endoscopy; optical sectioning; local drug delivery; tumors; in vivo testing

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MDPI and ACS Style

Liu, G.; Valvo, V.; Ahn, S.W.; Thompson, D.; Deans, K.; Kang, J.W.; Bhagavatula, S.; Dominas, C.; Jonas, O. A Two-Photon Microimaging-Microdevice System for Four-Dimensional Imaging of Local Drug Delivery in Tissues. Int. J. Mol. Sci. 2021, 22, 11752. https://doi.org/10.3390/ijms222111752

AMA Style

Liu G, Valvo V, Ahn SW, Thompson D, Deans K, Kang JW, Bhagavatula S, Dominas C, Jonas O. A Two-Photon Microimaging-Microdevice System for Four-Dimensional Imaging of Local Drug Delivery in Tissues. International Journal of Molecular Sciences. 2021; 22(21):11752. https://doi.org/10.3390/ijms222111752

Chicago/Turabian Style

Liu, Guigen, Veronica Valvo, Sebastian W. Ahn, Devon Thompson, Kyle Deans, Jeon Woong Kang, Sharath Bhagavatula, Christine Dominas, and Oliver Jonas. 2021. "A Two-Photon Microimaging-Microdevice System for Four-Dimensional Imaging of Local Drug Delivery in Tissues" International Journal of Molecular Sciences 22, no. 21: 11752. https://doi.org/10.3390/ijms222111752

APA Style

Liu, G., Valvo, V., Ahn, S. W., Thompson, D., Deans, K., Kang, J. W., Bhagavatula, S., Dominas, C., & Jonas, O. (2021). A Two-Photon Microimaging-Microdevice System for Four-Dimensional Imaging of Local Drug Delivery in Tissues. International Journal of Molecular Sciences, 22(21), 11752. https://doi.org/10.3390/ijms222111752

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