3D electron microscopy for analyzing nanoparticles in the tumor endothelium

• 成果类型: Article
• 署名作者: Mladjenovic, Stefan M.; Chandok, Ishaan S.; Darbandi, Ali; Nguyen, Luan N. M.; Stordy, Benjamin; Zhen, Mei; Chan, Warren C. W.
• 署名单位: University of Toronto; University of Toronto; Harvard University; Harvard University; University of Toronto; Sinai Health System Toronto; Lunenfeld Tanenbaum Research Institute; University of Toronto; Hospital for Sick Children (SickKids); Massachusetts Institute of Technology (MIT); University of Toronto; Nanyang Technological University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-11096
• DOI: 10.1073/pnas.2406331121
• 发表日期: 2024-12-10
• 关键词: blood-vessels; cells; liposomes

摘要

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 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 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 similar to 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 (similar to 66x increase). These surprising results suggest the need to increase vesicle encapsulation efficiency for improved transport and they provide provide unique insights into the interactions between medical agents, drug carriers, emerging materials, and cells at the single- nanoparticle level throughout tissues.