Therapeutic Targeting of Macrophages using Engineered Nanoparticles

Macrophages are versatile plastic cells that are key components of the body’s immune system. The interaction of engineered nanoparticles with macrophages is important because these cells clear nanoparticles from the circulation, and because they are potential therapeutic targets in inflammatory conditions, atherosclerosis and cancer. Therefore, an understanding of the features of engineered nanoparticles that influence their interaction with macrophages may allow optimization of their properties for enhanced drug delivery and imaging.
In the first part of this talk I will present results from a study where I showed that particle shape impacts phagocytosis by macrophages, and more importantly, that particle shape and size separately impact attachment and internalization. The study provides methodology for further exploring how particle shape can be controlled to achieve desired attachment and internalization. The results of the study also give mechanistic guidance on how particle shape can be manipulated to design drug carriers to evade macrophages, or alternatively to target macrophages.
In the second part, I will present results from a study where I investigated an alternate therapy for cancer by targeting and killing tumor associated macrophages (TAMs) that promotes tumor growth and metastasis. For this project, I designed nanoparticles that are loaded with an anti-macrophage drug and are actively targeted to TAMs in a mouse model of tumor and showed that these nanoparticles can selectively abrogate TAMs which leads to a suppression in tumor growth.