Nanomedicine Targeting to Activated Neutrophils and Neutrophil-Platelet Complexes Provides Effective Thromboprotection
Dillon Bohinc, Ph.D.
Case Western Reserve University
Cleveland, Ohio, U.S.
On Monday, July 19, 2021, Dillon Bohinc of Case Western Reserve University School of Medicine in Cleveland presented results from research aimed at developing a therapeutic strategy that specifically targets activated, pathogenic neutrophil subsets without the ubiquitous inhibition of resting cells. Why? Research to date has suggested that the functional characterization of neutrophils isolated from individuals with chronic inflammatory states has shown a distinct subpopulation that exhibits a pro-inflammatory, activated phenotype with prolonged life span and susceptibility to form neutrophil extracellular traps. Unrestricted recruitment and function of activated neutrophils can prolong inflammation and contribute to the development of pathologic conditions such as vascular thrombosis, tumor progression, autoimmune diseases, and chronic, nonhealing wounds.
Bohinc stated that this novel nanomedicine platform uniquely utilizes peptide surface decorations to confer binding specificity to neutrophil elastase on activated neutrophils and P-selectin on activated platelets. In proof-of-principle studies, Bohinc and colleagues demonstrated that this unique targeted delivery strategy can effectively deliver therapeutic cargo at sites of a developing clot and significantly reduced thrombus weights in vivo, in a model of murine DVT. These results can be applied to several neutrophil-driven pathologies and minimize off-target effects associated with systemic drug administration and global inhibition of neutrophil functions.