Conference proceeding
Pulmonary Marginated Neutrophils: A Novel Target for Vascular Targeted Nanoparticles
01 Jan 2022
Abstract
Pulmonary disease is one of the leading causes of mortality in the world, and continues to remain in need of effective therapies. To address this need, nanomedicine is a promising strategy that achieves organ specific delivery of RNA and small molecular drugs. Antibody conjugated nanoparticles targeting vascular endothelial moieties such as ICAM, PLVAP and PECAM can concentrate drugs in the lungs up to 300 fold more than standard drug delivery. However, for decades, this organ specificity had been assumed to be solely due to endothelial cell specific uptake in the pulmonary vasculature. Thus, in our study, we sought to determine the cell type specificity of vascular targeted liposomes. We achieved this by conjugating antibodies targeting ICAM, PECAM and PLVAP, and delivered them intravenously in both healthy mice and mice with acute lung injury. Surprisingly, we found that in addition to endothelial cell uptake, there was avid uptake by marginated neutrophils in both healthy and diseased mice. Across the vascular targeting moieties, PLVAP had the most endothelial specific uptake though there was still some uptake by marginated neutrophils. To further understand the mechanisms of uptake, we showed that marginated neutrophil liposome uptake is not mediated by surface presentation of ICAM and PECAM as previously thought. Furthermore, we demonstrated that the mechanism of uptake is similar amongst other forms of vascular targeted conjugated nanoparticles. Finally, we showed that these mechanisms of liposomal uptake can be recapitulated in human lungs. In conclusion, from our data, cell specific targeting remains elusive and will require further engineering to improve specificity. However, neutrophil nanoparticle uptake does present a unique opportunity for innovative drug delivery strategies to ameliorate lung disease.
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Details
- Title
- Pulmonary Marginated Neutrophils: A Novel Target for Vascular Targeted Nanoparticles
- Creators
- Eno-Obong EssienMarco ZamoraAditi MurthyElizabeth HoodLaura FergusonOscar Marcos-ContrerasJacob S. Brenner
- Publisher
- figshare
- Resource Type
- Conference proceeding
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Other Identifier
- 991021811737304721