Nanoparticles target anti-inflammatory drugs where needed

Researchers at the University of Illinois at Chicago have developed a system for precisely delivering anti-inflammatory drugs to immune cells gone out of control, while sparing their well-behaved counterparts. Their findings were published online Feb. 23 in Nature Nanotechnology. The system uses nanoparticles made of tiny bits of protein designed to bind to unique receptors found only on neutrophils, a type of immune cell engaged in detrimental acute and chronic inflammatory responses.

In a normal immune response, neutrophils circulating in the blood respond to signals given off by injured or damaged blood vessels and begin to accumulate at the injury, where they engulf bacteria or debris from injured tissue that might cause infection. In chronic inflammation, neutrophils can pile up at the site of injury, sticking to the blood vessel walls and to each other and contributing to tissue damage.

Adhesion of neutrophils to blood vessel walls is a major factor in acute lung injury, where it can impair the exchange of gases between the lungs and blood, leading to severe breathing problems. If untreated, the disease has a 50 percent mortality rate in intensive care units.

Corticosteroids and non-steroidal anti-inflammatory drugs used to treat inflammatory diseases are "blunt instruments that affect the whole body and carry some significant side effects," says Asrar B. Malik, the Schweppe Family Distinguished Professor and head of pharmacology in the UIC College of Medicine, who is lead author of the paper.

Neutrophils that are stuck to blood vessels or clumped together have unique receptors on their surface that circulating neutrophils lack. Malik and his colleagues designed a nanoparticle to take advantage by embedding it with an anti-inflammatory drug. The nanoparticles bind to the receptors, and the neutrophils internalize the nanoparticle. Once inside, the anti-inflammatory drug works to "unzip" the neutrophil and allow it to re-enter the bloodstream.

"The nanoparticle is very much like a Trojan horse," Malik said. "It binds to a receptor found only on these activated, sticky neutrophils, and the cell automatically engulfs whatever binds there. Because circulating neutrophils lack these receptors, the system is incredibly precise and targets only those immune cells that are actively contributing to inflammatory disease."

Malik, along with research assistant professor Zhenjia Wang and assistant professor Jaehyung Cho, used intra-vital microscopy to follow nanoparticles in real-time in mice with induced vascular inflammation. The nanoparticles were labeled with a fluorescent dye, and could be seen binding to and entering neutrophils clustered together on the inner walls of capillaries, but not binding to freely circulating neutrophils. If the researchers attached a drug called piceatannol, which interferes with cell-cell adhesion, to the nanoparticles, they observed that clusters of neutrophils that took up the particles detached from each other and from the blood vessel wall. The cells were in effect neutralized and could no longer contribute to inflammation at the site of an injury.

The findings, Malik said, "show that nanoparticles can be used to deliver drugs in a highly targeted, specific fashion to activated immune cells and could be designed to treat a broad range of inflammatory diseases."

Jing Li, postdoctoral research associate in pharmacology, was also a co-author of the study.

The research was supported by grants 11SDG7490013 from the American Heart Association, and grants K25HL11157, R01 HL109439 and P01 HL77806 from the National Institutes of Health.

Most Popular Now

FDA grants Breakthrough Therapy Designation to Pfi…

Pfizer Inc. (NYSE:PFE) today announced that its investigational Group B Streptococcus (GBS) vaccine candidate, GBS6 or PF-06760805, received Breakthrough Therapy Designat...

Novartis invests in early technical development ca…

Novartis today announced it is investing in next-generation biotherapeutics with the creation of a fully integrated, dedicated USD 300m scientific environment that will b...

Pfizer and BioNTech receive positive CHMP opinion …

Pfizer Inc. (NYSE: PFE) and BioNTech SE (Nasdaq: BNTX) announced a 30-µg booster dose of their Omicron BA.4/BA.5 bivalent-adapted COVID-19 vaccine (COMIRNATY® Original/Om...

Malaria booster vaccine shows durable high efficac…

Researchers from the University of Oxford and their partners have today reported new findings from their Phase 2b trial following the administration of a booster dose of ...

Strict COVID lockdowns in France improved cardiova…

A new paper in European Heart Journal - Digital Health, published by Oxford University Press, indicates that social-distancing measures like total lockdown have a measura...

U.S. clinical trial evaluating antiviral for monke…

A Phase 3 clinical trial evaluating the antiviral tecovirimat, also known as TPOXX, is now enrolling adults and children with monkeypox infection in the United States. St...

Stem cell-gene therapy shows promise in ALS safety…

Cedars-Sinai investigators have developed an investigational therapy using support cells and a protective protein that can be delivered past the blood-brain barrier. This...

Drug turns cancer gene into "eat me" fla…

Tumor cells are notoriously good at evading the human immune system; they put up physical walls, wear disguises and handcuff the immune system with molecular tricks. Now...

Mucosal antibodies in the airways protect against …

High levels of mucosal antibodies in the airways reduce the risk of being infected by omicron, but many do not receive detectable antibodies in the airways despite three ...

WHO grants prequalification to GSK's Mosquirix - t…

GSK plc (LSE/NYSE: GSK) announced that the World Health Organization (WHO) has awarded prequalification to Mosquirix (also known as RTS,S/AS01), GSK's groundbreaking mala...

Bird's enzyme points toward novel therapies

Thank the rare crested ibis for a clue that could someday help our bodies make better drugs. The species of bird is the only one known to naturally produce an enzyme ...

WHO strongly advises against antibody treatments f…

The antibody drugs sotrovimab and casirivimab-imdevimab are not recommended for patients with COVID-19, says a WHO Guideline Development Group of international experts in...