EAST LANSING, Mich. & STANFORD, Calif.—Being eaten away by nanoparticles from the inside out sounds like a gruesome science fiction movie fate, but it come across as a lot less horrifying when the nanoparticles in question are devouring a threat to cardiovascular health.
Specifically, Michigan State University (MSU) researchers in partnership with a team at Stanford University have created Trojan horse-style nanoparticles that can eat away—from the inside out—portions of plaques that are known to cause heart attacks, thus providing a potential new therapy for atherosclerosis.
The results of this work, published in Nature Nanotechnology, describe in part how the nanoparticle can be precisely directed to atherosclerotic plaque due to its high selectivity to a particular immune cell type—monocytes and macrophages. After the nanoparticles insert themselves inside the macrophages of such plaques, they release a drug that allows them to remove dead and diseased cells at the core of the plaque—basically eating up the cellular debris. As summarized by Bryan Smith, an associate professor of biomedical engineering at MSU, “By reinvigorating the macrophages, plaque size is reduced and stabilized.”
And if you want to get a bit more technical about what makes up these plaque-eaters, the paper explains that, “The system, termed SWNT-SHP1i, involves a backbone of polyethylene glycol (PEG)-functionalized single-walled carbon nanotubes (SWNTs) loaded with (1) a fluorescent probe Cy5.5 and (2) a small-molecule inhibitor of CD47’s downstream effector molecule, SHP-1.”
Similar types of studies previously have acted on the surface of the cells, according to MSU, but
Smith’s work focused on intercepting the signaling of the receptors in the macrophages and sending a message via small molecules using nano-immunotherapeutic platforms. MSU reports that this new approach works intracellularly and has been effective in stimulating macrophages.
As the paper notes of this nanoparticle (NP) approach, “The advent of modifiable, macrophage-specific NPs therefore represents a significant advance in the fight against atherosclerosis. Although NPs have been developed for imaging and the treatment of atherosclerosis, the lack of sufficient selectivity of the NP to the target cell (for example, inflammatory monocytes) and desired end organ has hampered their efficacy and utility.”
“We found we could stimulate the macrophages to selectively eat dead and dying cells—these inflammatory cells are precursor cells to atherosclerosis—that are part of the cause of heart attacks,” Smith elaborated. “We could deliver a small molecule inside the macrophages to tell them to begin eating again.”
Smith said that future clinical trials on the nanoparticle are expected to reduce the risk of most types of heart attacks, with minimal side effects due to the unprecedented selectivity of the nanodrug.
An approach like this also has potential beyond atherosclerosis.
Noted Smith: "We were able to marry a groundbreaking finding in atherosclerosis by our collaborators with the state-of-the-art selectivity and delivery capabilities of our advanced nanomaterial platform. We demonstrated the nanomaterials were able to selectively seek out and deliver a message to the very cells needed. It gives a particular energy to our future work, which will include clinical translation of these nanomaterials using large animal models and human tissue tests. We believe it is better than previous methods.”
Smith has filed a provisional patent and will begin marketing it later this year.
And it is worth pointing out that, as with all things, there is room for improvement: “Although our current and previous studies demonstrate the remarkable selectivity of SWNTs for monocytes and macrophages, further understanding of the mechanism of SWNT selectivity and incorporation of molecular targeting ligands may enable a more efficient delivery to the diseased site, or even to specific macrophage subsets,” the paper's authors conclude. “As the SWNT backbone can be modified to deliver multiple therapeutic agents into the same cell, future studies should determine whether bispecific nanoimmunotherapies that simultaneously target efferocytosis and other aspects of macrophage biology (for example, cholesterol efflux and macrophage skewing) might have a synergistic effect.”