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Pro-efferocytic nanoparticles are specifically taken up by lesional macrophages and prevent atherosclerosis.
- Source :
-
Nature nanotechnology [Nat Nanotechnol] 2020 Feb; Vol. 15 (2), pp. 154-161. Date of Electronic Publication: 2020 Jan 27. - Publication Year :
- 2020
-
Abstract
- 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-SIRPĪ± 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.
- Subjects :
- Animals
CD47 Antigen metabolism
Cardiovascular Agents chemistry
Cardiovascular Agents pharmacology
Disease Models, Animal
Female
Male
Mice, Transgenic
Nanomedicine methods
Protein Tyrosine Phosphatase, Non-Receptor Type 6 antagonists & inhibitors
Protein Tyrosine Phosphatase, Non-Receptor Type 6 metabolism
Receptors, Immunologic metabolism
Atherosclerosis metabolism
Macrophages drug effects
Macrophages metabolism
Nanotubes, Carbon
Phagocytosis drug effects
Signal Transduction drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1748-3395
- Volume :
- 15
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Nature nanotechnology
- Publication Type :
- Academic Journal
- Accession number :
- 31988506
- Full Text :
- https://doi.org/10.1038/s41565-019-0619-3