3D electron microscopy for analyzing nanoparticles in the tumor endothelium.

Autor:	Mladjenovic SM; Institute of Biomedical Engineering, University of Toronto, Toronto, ON M5S 3G9, Canada.; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada., Chandok IS; Department of Physics, Harvard University, Cambridge, MA 02138.; Center for Brain Science, Harvard University, Cambridge, MA 02138.; Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON M5P 1X5., Darbandi A; Nanoscale Biomedical Imaging Facility, Hospital for Sick Children, Toronto, ON M5G1H3, Canada., Nguyen LNM; Institute of Biomedical Engineering, University of Toronto, Toronto, ON M5S 3G9, Canada.; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada.; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139., Stordy B; Institute of Biomedical Engineering, University of Toronto, Toronto, ON M5S 3G9, Canada.; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada., Zhen M; Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON M5P 1X5., Chan WCW; Institute of Biomedical Engineering, University of Toronto, Toronto, ON M5S 3G9, Canada.; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada.; Department of Chemistry, University of Toronto, Toronto, ON M5S 3H6, Canada.; School of Chemistry, Chemical Engineering, and Biotechnology, Nanyang Technological University, 637371, Singapore.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2024 Dec 17; Vol. 121 (51), pp. e2406331121. Date of Electronic Publication: 2024 Dec 12.
DOI:	10.1073/pnas.2406331121
Abstrakt:	Delivering medical agents to diseased tissues has been challenging, leading researchers to study the in vivo transport process in the body for improving delivery. Many imaging techniques exist for mapping the distribution of medical agent-carrying nanoparticles in tissues, but they cannot capture the three-dimensional context of tissues with single nanoparticle resolution. Here, we developed 3DEM-NPD, a three-dimensional electron microscopy (3D EM) machine learning strategy to image and map single nanoparticle distributions (NPD) in tissues. 3DEM-NPD provides unbiased visualization and quantification of individual nanoparticles within organs. We applied this technique to quantify nanoparticle transport through tumor blood vessel endothelial cells. We measured the cell diameter, surface area, and volume and found that traditional 2D EM cannot accurately measure these features. We used machine learning to locate over 550,000 nanoparticles in less than 3 h with an accuracy of over 82%. The 3DEM-NPD method allowed us to establish a metric to quantify nanoparticle transport at the single nanoparticle level and to quantify the morphological features of ~2,800 vesicles. We find that on average there are only 2.4 nanoparticles per vesicle with a theoretical maximum of 158 nanoparticles per vesicle (~66x increase). These surprising results suggest the need to increase vesicle encapsulation efficiency for improved transport and they provide a benchmark for increasing nanoparticle transport and delivery. This technique may provide unique insights into the interactions between medical agents, drug carriers, emerging materials, and cells at the single-nanoparticle level throughout tissues. Competing Interests: Competing interests statement:W.C.W.C. is a co-founder of Luna Nanotech and consults for Foresite Capital, the Cystic Fibrosis Foundation, METiS Therapeutics, Moderna and Merck.
Databáze:	MEDLINE
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