Complement C3-dependent uptake of targeted liposomes into human macrophages, B cells, dendritic cells, neutrophils, and MDSCs

What is it about?

We have developed a method to target and deliver compounds to the myeloid cells of the immune system. These cells are important for initial detection of foreign particles, such as bacteria or tumor antigens. They engulf these particles and express them to effector cells of the immune system (mainly T cells) for specific recognition and destruction of those foreign elements. Our lab has developed a liposomal method to target these cell types. Liposomes are beneficial for delivery of compounds because they have low toxicity and are tolerated well by the body. They allow for encapsulation of both hydrophobic and hydrophilic compounds due to their amphipathic nature, as well as provide protection to the encapsulated compound. We have attached a molecule to the surface of our liposomes that binds to specific proteins in serum, which then allows them to be targeted to cells which contain a receptor for that protein. Using flow cytometry, a method that sorts samples into single cells, we have identified the main populations of cells that are targeted by our liposomes: dendritic cells, macrophages, B cells, myeloid derived suppressor cells, and neutrophils. These cells are all myeloid cells which contain receptors for the serum proteins to which the liposomes are attached. This system involving liposomes and serum proteins provides a targeting and delivery method that has low toxicity, high specificity, and low production cost.

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Why is it important?

The majority of the cell types that our system targets are antigen presenting cells. These cells initiate immune recognition of tumor antigen by displaying antigen to effector cells. We are also able to target several cell types that suppress the immune response against tumors. To create effective cancer immunotherapies, it is critical that we can target the suppressive cell types of the immune system with immunostimulatory compounds, as well as deliver tumor antigen to the antigen presenting cells. The combination of these two methods would produce a robust and effective treatment.