Scientists have developed nanomedicines that can deliver drug packets directly to lesions in diseased arteries, acting like nano-sized ‘drones’ to target atherosclerosis, a major risk factor for deaths caused by heart attack or stroke.
Atherosclerosis – in which arteries become narrowed due to a buildup of fatty substance that forms a plaque or atheroma – can affect the coronary arteries supplying the heart. Such coronary disease is the number one killer in the US, resulting in a quarter of all deaths.
In their study, which is published online by Science Translational Medicine, Dr. Omid Farokhzad and colleagues successfully restructured atherosclerotic plaques in mice to make them more stable – by targeting them with biodegradable nanomedicines.
“This is the first example of a targeted nanoparticle technology that reduces atherosclerosis in an animal model,” says Dr. Farokhzad, associate professor and director of the laboratory of nanomedicine and biomaterials at Brigham and Women’s Hospital and Harvard Medical School, both in Boston, MA. Dr. Farokhzad adds:
“We observed a clear benefit from the nanomedicine that led to a stabilized plaque that, similar to the condition in humans, would be less likely to rupture and cause heart attacks. Additionally, we observed drastic changes in key clinical hallmarks of advanced atherosclerosis.”
The targeted nanomedicines were nanoengineered to carry an anti-inflammatory drug payload in the form of a biomimetic peptide derived from one of the body’s own natural anti-inflammatory proteins called Annexin A1.
The design was such that this biological therapeutic could be released at the target atherosclerotic plaques in a controlled manner.
In mice with advanced atherosclerosis the nanomedicines were compared with controls, and after 5 weeks of treatment, artery damage “was significantly repaired and plaque was stabilized.”
The researchers observed that the nanomedicine-treated mice, compared with those given empty nanoparticles, showed:
- Reduction in reactive oxygen species
- Increase in collagen, strengthening the fibrous cap of atherosclerotic plaques, which can otherwise rupture
- Reduction of the plaque necrotic core.
Reducing inflammation is an approach taken by many, say the researchers, but one that can mean drugs are taken “for years, even decades.”
If the anti-inflammatory drug is not targeted, but distributed throughout the body, it “will also impair the immune system’s ability to fight infection,” says co-senior author Dr. Ira Tabas, the Richard J. Stock professor of medicine (immunology) and professor of pathology and cell biology at Columbia University Medical Center, New York.
Taking drugs with side-effects for many years to prevent a heart attack that might not have happened anyway, “may not be worth the risk.”
Reducing inflammation does not address any damage already done, either, whereas the nanoparticles in this study – being 1,000 times smaller than the tip of a single human hair – were able to get underneath atherosclerotic plaques to effect repair.
The nanomedicines “were shown to be capable of maneuvering through the blood circulation, and traversing leaky regions through to the inside of the plaques, as was demonstrated by fluorescence microscopy imaging of the plaque lesions,” say the researchers.
“In addition to their specific ‘sticky’ surfaces, their small sub-100 nanometer size is also a key property that facilitates the retention and accumulation of these nanoparticles within the plaques.”
Co-lead author Nazila Kamaly, PhD, instructor working with Dr. Farokhzad in the laboratory of nanomedicine and biomaterials at Brigham and Harvard, explains that while the technology is yet to be tested in humans, its properties lend well to clinical development.
“These nanomedicines are developed using biodegradable polymers that can break-up over time in the body using the body’s natural mechanisms,” Dr. Kamaly says, “and can be nanoengineered using scalable chemistries and nanotechnologies, which ultimately can facilitate their rapid translation to the clinic.”
Dr. Tabas says:
“In this study, we’ve shown, for the first time, that a drug that promotes resolution of inflammation and repair is a viable option, when the drug is delivered directly to plaques via nanoparticles.”
Dr. Tabas believes there is further potential than that already shown in the study: “We think that we can obtain even better delivery to plaques and improve healing more than with the current peptides.” The team is excited about the wider application of their research in nanomedicine.
“I’m optimistic that with additional animal validation we will also consider the human testing of the inflammation-resolving targeted nanoparticles for a myriad of unmet medical needs,” says Dr. Farokhzad. “These are exciting times in medicine, and the future of nanomedicine is incredibly bright.”
Dr. Farokhzad adds: “The inflammation-resolving targeted nanoparticles have shown exciting potential not only for the potential treatment of atherosclerosis as described here, but also other therapeutic areas, including wound repair, for example.”