Interaction of Lipid Nanoparticles with Pulmonary Innate Immune Cells in the Context of ARDS

Tuesday, May 2, 2023

9:30 AM-11:30 AM

BIOMED PhD Research Proposal

Title:
Interaction of Lipid Nanoparticles with Pulmonary Innate Immune Cells in the Context of Acute Respiratory Distress Syndrome (ARDS)

Speaker:
Marco Zamora, PhD Candidate
School of Biomedical Engineering, Science and Health Systems
Drexel University

Advisors:
Jacob S. Brenner, MD, PhD
Assistant Professor
Perelman School of Medicine
Associate Director, Penn Health-Tech
University of Pennsylvania

Kara L. Spiller, PhD
Professor
School of Biomedical Engineering, Science and Health Systems
Drexel University

Details:
Dozens of small molecule drugs have undergone clinical trials for the treatment of acute respiratory distress syndrome (ARDS), but all of them have failed. Liposomes and nucleic acid lipid nanoparticles (LNPs) are both FDA-approved nanoparticles that have the potential to address failures to deliver therapeutics for this disease.

These nanocarriers can: 1) deliver multiple small molecule drugs and nucleic acids capable of acting on multiple pathways. 2) achieve localization either by surface coating with antibodies that bind to epitopes (ICAM, PECAM, or PLVAP) on alveolar endothelial cells, or by modification of a nanoparticle’s surface chemistry to alter the tropism of the nanoparticle, strongly concentrating their cargo to the site of pathology, and thereby drastically decreasing side-effects.

While these particles have been shown to achieve high localization to the lung1-3, the kinetics as well as the cell types that actively take up these nanoparticles, have not been rigorously characterized, especially in the context of acute disease. As such, our central hypothesis is that nanoparticles (NPs) are promising, but the traditional view that these NPs only go to endothelial cells is incorrect, and impacts NP side effects and efficacy.

As a first step, our lab has already established an in vivo model of ARDS-like injury, nebulized LPS (neb-LPS). We will use this model to determine the cell types that take up antibody-targeted liposomes in healthy and acute injured animals  as well as map out the kinetics of clearance. We will then use similar techniques to assess two methods for LNP localization to the lung, antibody-mediated targeting and physicochemical tropism (Aim 3). We will determine the cell types that 1) take up these nanoparticles and 2) express the mRNA cargo. Additionally, we will determine how this changes in the context of acute inflammation using the neb-LPS model.

Contact Information

Natalia Broz
njb33@drexel.edu