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Nanotherapeutic Shots through the Heart of Plaque

Yogendra Kanthi1,2, Adam de la Zerda3,4,5,6,7, Bryan Ronain Smith8,9

  • 1Division of Cardiovascular Medicine, Frankel Cardiovascular Center , University of Michigan , Ann Arbor , Michigan 48109 , United States.

ACS Nano
|January 28, 2020
PubMed

Insights

Nanoparticle delivery for cardiovascular disease is improving. Atherosclerosis progression and metabolic therapy can limit nanoparticle entry into plaques, highlighting the need for advanced imaging to optimize nanodrug delivery for better clinical translation.

Area of Science:

  • Cardiovascular Disease Research
  • Nanomedicine
  • Biomedical Imaging

Background:

  • Nanoparticulate drug applications have advanced significantly in cancer but lag in cardiovascular disease.
  • Optimizing nanodrug delivery for cardiovascular diseases requires understanding nanoparticle kinetics in atherosclerotic plaques.
  • Endothelial barrier integrity plays a crucial role in nanoparticle delivery via the enhanced permeation and retention (EPR) effect.

Purpose of the Study:

  • To investigate the impact of atherosclerosis progression and metabolic therapy on nanoparticle entry into plaques.
  • To explore advanced dynamic intravital microscopy for mechanistic studies of nanoparticle extravasation.
  • To evaluate the potential of combining metabolic therapy with efferocytosis stimulation for cardiovascular disease treatment.

Main Methods:

  • Utilizing super-resolution and correlative light/electron microscopy to study endothelial barrier function.
  • Employing dynamic intravital microscopy to analyze nanoparticle kinetics in atherosclerotic plaques.
  • Examining the interplay between atherosclerosis, metabolic therapy, and nanoparticle uptake.

Main Results:

  • Atherosclerotic plaque progression was found to stabilize endothelial junctions, potentially reducing nanoparticle entry.
  • Metabolic therapy may induce similar effects on endothelial junctions as atherosclerosis progression.
  • Free extravasation versus immune-mediated uptake influences nanoparticle delivery efficacy.

Conclusions:

  • Understanding nanoparticle-plaque interactions is critical for advancing nanomedicine in cardiovascular diseases.
  • Advanced microscopy techniques are essential for elucidating mechanisms of nanodrug delivery.
  • Combining metabolic therapy with efferocytosis stimulation shows promise for enhancing atherosclerotic plaque regression.

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