Unique Nanoparticle Platform Developed to Target Activated Neutrophils Linked Diabetes, Cancer, Vascular Thrombosis

Researchers from Case Western Reserve recently designed a nanoparticle platform targeting disease-related activated neutrophils exclusively while leaving inactive circulating neutrophils untouched.

As specified in a Phys.org report, neutrophils are a white blood cell type that helps combat diseases by traveling to the infected area of the body to seek and destroy harmful pathogens.

Nonetheless, left unrestricted, neutrophils can also prolong inflammation and add to the development of certain conditions such as cancer, diabetic retinopathy, and vascular thrombosis.

According to Evi Stavrou, a CWRU professor, the newly developed platform guarantees that the "disease-associated neutrophils are suppressed," although their ability to combat infections stays intact.

Potentially Transforming Treatments for Prevailing Diseases

Findings of the study published in Nature Nanotechnology offer the possibility of transforming treatments for prevalent diseases, which include complications from diabetes, cancer, and autoimmune disorders.

Stavrou, the Oscar D. Ratnoff Designated Professor in Medicine and Hematology at the School of Medicine, is the study's lead corresponding author.

Their results appeared from a three-year collaboration among the lab of Stavrou, colleagues at Case Western Reserve's biomedical engineering and pharmacology departments, and research partners worldwide.

Biomedical engineering professor Anirban Sen Gupta and Professor of Engineering Leonard Case Jr. at the Case School of Engineering said this collaboration between the lab of Dr. Stavrou and their lab brings the complementary and interdisciplinary expertise together to develop a unique nanomedicine platform that allows specific targeting of activated neutrophils,

Unusual Neutrophil Activity

A similar WhatsNew2day report describes the unusual neutrophil activity as "emerging as a major mechanism in numerous diseases," and this platform can enable targeted treatment of such illnesses minus compromising the immune defense capabilities of the neutrophil.

The team's work demonstrated that targeting a neutrophil-suppressing drug, particularly to the disease site, by packaging it in a nanoplatform increased the drug's effectiveness.

Doing so also decreased the toxic impacts compared to when the drug is directly intravenously administered.

The study depicts the first demonstration of active targeting of what are identified as neutrophil "sub-populations." Moreover, their platform is flexible enough to be tailored to certain neutrophil populations, either alone or in cell complexes, explained Stavrou.

Focus on Neutrophil Estate

To target activated neutrophils, in particular, Stavrou and Sen Gupta initially needed to identify a surface marker distinctly expressed by stimulated neutrophils, although not by resting cells.

Specifically, the team focused on neutrophil elastase secreted by neutrophils during inflammation since neutrophils only generate it and only travel the cell's surface when activated.

To use NE as "bait" for nanoparticle binding, Stavrou and Sen Gupta developed a peptide emanated from alpha-1 antitrypsin, a natural neutrophil elastase inhibitor, and demonstrated its particular binding ability toward NE.

Designing the nanoparticle surface with this peptide allowed its particular binding to activated neutrophils.

Therapeutic Nanoparticles

Following this, pharmacologic inhibitors interfering with neutrophil functions were selected. Incorporating these two components on a lipid NP platform produced active neutrophil-targeted therapeutic nanoparticles.

Furthermore, the assembled nanoparticles were used in in vitro and in vitro tests to define their biodistribution, loading ability, particularly toward NE, and circulation lifetime in rodent models.

A lot of variations of NPs were developed that can particularly interact with activated neutrophils only or with stimulated neutrophils that are complex with other cells like activated platelets, a hallmark of inflammatory thrombosis in various illnesses.

Related information about nanomedicine is shown on Singularity University Summits' YouTube video below:

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