Pro-efferocytic nanoparticles are specifically taken up by lesional macrophages and prevent atherosclerosis

Nat Nanotechnol. 2020 Feb;15(2):154-161. doi: 10.1038/s41565-019-0619-3. Epub 2020 Jan 27.


Atherosclerosis is the process that underlies heart attack and stroke. A characteristic feature of the atherosclerotic plaque is the accumulation of apoptotic cells in the necrotic core. Prophagocytic antibody-based therapies are currently being explored to stimulate the phagocytic clearance of apoptotic cells; however, these therapies can cause off-target clearance of healthy tissues, which leads to toxicities such as anaemia. Here we developed a macrophage-specific nanotherapy based on single-walled carbon nanotubes loaded with a chemical inhibitor of the antiphagocytic CD47-SIRPα signalling axis. We demonstrate that these single-walled carbon nanotubes accumulate within the atherosclerotic plaque, reactivate lesional phagocytosis and reduce the plaque burden in atheroprone apolipoprotein-E-deficient mice without compromising safety, and thereby overcome a key translational barrier for this class of drugs. Single-cell RNA sequencing analysis reveals that prophagocytic single-walled carbon nanotubes decrease the expression of inflammatory genes linked to cytokine and chemokine pathways in lesional macrophages, which demonstrates the potential of 'Trojan horse' nanoparticles to prevent atherosclerotic cardiovascular disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Atherosclerosis / metabolism*
  • CD47 Antigen / metabolism
  • Cardiovascular Agents / chemistry
  • Cardiovascular Agents / pharmacology
  • Disease Models, Animal
  • Female
  • Macrophages* / drug effects
  • Macrophages* / metabolism
  • Male
  • Mice, Transgenic
  • Nanomedicine / methods
  • Nanotubes, Carbon*
  • Phagocytosis / drug effects*
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6 / antagonists & inhibitors
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6 / metabolism
  • Receptors, Immunologic / metabolism
  • Signal Transduction / drug effects*


  • CD47 Antigen
  • Cardiovascular Agents
  • Cd47 protein, mouse
  • Nanotubes, Carbon
  • Ptpns1 protein, mouse
  • Receptors, Immunologic
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6
  • Ptpn6 protein, mouse