A hyperspectral method to assay the microphysiological fates of nanomaterials in histological samples

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Abstract

Nanoparticles are used extensively as biomedical imaging probes and potential therapeutic agents. As new particles are developed and tested in vivo, it is critical to characterize their biodistribution profiles. We demonstrate a new method that uses adaptive algorithms for analysis of hyperspectral dark-field images to study the interactions between tissues and administered nanoparticles. This non-destructive technique quantitatively identifies particles in ex vivo tissue sections and enables detailed observations of accumulation patterns arising from organ-specific clearance mechanisms, particle size, and the molecular specificity of nanoparticle surface coatings. Unlike nanoparticle uptake studies with electron microscopy, this method is tractable for imaging large fields of view. Adaptive hyperspectral image analysis achieves excellent detection sensitivity and specificity and is capable of identifying single nanoparticles. Using this method, we collected the first data on the sub-organ distribution of several types of gold nanoparticles in mice and observed localization patterns in tumors.

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Elliott D SoRelle

Molecular Imaging Program at Stanford, Stanford University, Stanford, United States

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-3362-1028
Orly Liba

Molecular Imaging Program at Stanford, Stanford University, Stanford, United States

Competing interests
The authors declare that no competing interests exist.
Jos L Campbell

Ian Potter NanoBioSensing Facility, NanoBiotechnology Research Laboratory, School of Science, RMIT University, Melbourne, Australia

Competing interests
The authors declare that no competing interests exist.
Roopa Dalal

Department of Ophthalmology, Stanford University, Stanford, United States

Competing interests
The authors declare that no competing interests exist.
Cristina L Zavaleta

Molecular Imaging Program at Stanford, Stanford University, Stanford, United States

Competing interests
The authors declare that no competing interests exist.
Adam de la Zerda

Molecular Imaging Program at Stanford, Stanford University, Stanford, United States

For correspondence
adlz@stanford.edu

Competing interests
The authors declare that no competing interests exist.

Funding

Claire Giannini Fund

Adam de la Zerda

Stanford Bio-X Interdisciplinary Initiative Seed Grant

Adam de la Zerda

U.S. Air Force (FA9550-15-1-0007)

Adam de la Zerda

National Institutes of Health (NIH DP50D012179)

Adam de la Zerda

Damon Runyon Cancer Research Foundation (DFS# 06-13)

Adam de la Zerda

Susan G. Komen (SAC15-00003)

Adam de la Zerda

Mary Kay Foundation (017-14)

Adam de la Zerda

Donald E. and Delia B. Baxter Foundation

Adam de la Zerda

Skippy Frank Foundation

Adam de la Zerda

Center for Cancer Nanotechnology Excellence and Translation (CCNE-T U54CA151459)

Adam de la Zerda

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All animal experiments in this study were performed in compliance with IACUC guidelines and with the Stanford University Animal Studies Committee's Guidelines for the Care and Use of Research Animals (APLAC Protocol #27499 and #29179).

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.