Label-Free Tomographic Imaging of Lipid Droplets in Foam Cells for Machine-Learning-Assisted Therapeutic Evaluation of Targeted Nanodrugs

Sangwoo Park, Jae Won Ahn, Youngju Jo, Ha Young Kang, Hyun Jung Kim, Yeongmi Cheon, Jin Won Kim, Yongkeun Park, Seongsoo Lee, Kyeongsoon Park

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Lipid droplet (LD) accumulation, a key feature of foam cells, constitutes an attractive target for therapeutic intervention in atherosclerosis. However, despite advances in cellular imaging techniques, current noninvasive and quantitative methods have limited application in living foam cells. Here, using optical diffraction tomography (ODT), we performed quantitative morphological and biophysical analysis of living foam cells in a label-free manner. We identified LDs in foam cells by verifying the specific refractive index using correlative imaging comprising ODT integrated with three-dimensional fluorescence imaging. Through time-lapse monitoring of three-dimensional dynamics of label-free living foam cells, we precisely and quantitatively evaluated the therapeutic effects of a nanodrug (mannose-polyethylene glycol-glycol chitosan-fluorescein isothiocyanate-lobeglitazone; MMR-Lobe) designed to affect the targeted delivery of lobeglitazone to foam cells based on high mannose receptor specificity. Furthermore, by exploiting machine-learning-based image analysis, we further demonstrated therapeutic evaluation at the single-cell level. These findings suggest that refractive index measurement is a promising tool to explore new drugs against LD-related metabolic diseases.

Original languageEnglish
Pages (from-to)1856-1865
Number of pages10
JournalACS Nano
Volume14
Issue number2
DOIs
Publication statusPublished - 2020 Feb 25

Keywords

  • 3-D holotomography
  • atherosclerosis
  • foam cell
  • lipid droplet
  • machine learning
  • refractive index

ASJC Scopus subject areas

  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)

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  • Cite this

    Park, S., Ahn, J. W., Jo, Y., Kang, H. Y., Kim, H. J., Cheon, Y., Kim, J. W., Park, Y., Lee, S., & Park, K. (2020). Label-Free Tomographic Imaging of Lipid Droplets in Foam Cells for Machine-Learning-Assisted Therapeutic Evaluation of Targeted Nanodrugs. ACS Nano, 14(2), 1856-1865. https://doi.org/10.1021/acsnano.9b07993