Besides cancer cells, tumors contain a vast array of non-cancerous cell types, which have been
largely overlooked as potential therapeutic targets and have been labeled “the forgotten half of
the tumor”. One of these non-cancerous cell types are a part of the immune system known as
macrophages. Certain macrophages undergo changes when they are present in the tumor
environment. These changes entail an overexpression of the Macrophage Mannose Receptor
(MMR) and the development of a strong protumoral activity. Macrophages which have undergone
these changes are referred to as Tumor Associated Macrophages (TAMs). These TAMs have also
been reported to reduce the effectiveness of current anti-cancer treatments, such has radiation
and chemotherapy. In this project, we aim to develop intelligent nanoparticles that can reprogram
these protumoral TAMs into an anti-tumoral phenotype. Hereto, we will encapsulate a drug
molecule capable of reprogramming TAMs inside polymeric nanoparticles which will degrade after
uptake by the macrophage. The use of nanoparticles will allow us to target the tumor, as
nanoparticles smaller than 200 nm exhibit enhanced tumor accumulation. To promote specific
uptake by TAMs, the nanoparticles will be engineered with a targeting ligand specific for the
overexpressed Macrophage Mannose Receptor.