Artificial white blood cells are typically membrane bound vesicles designed to mimic the immunomodulatory behavior of naturally produced leukocytes. While extensive research has been done with regards to artificial red blood cells and platelets for use in emergency blood transfusions, research into artificial white blood cells has been focused on increasing the immunogenic response within a host to treat cancer or deliver drugs in a more favorable fashion. While certain limitations have prevented leukocyte mimicking particles from becoming widely used and FDA approved, more research is being allocated to this area of synthetic blood which has the potential for producing a new form of treatment for cancer and other diseases.
Leukocyte Physiology
Leukocytes, otherwise known as white blood cells (WBCs), come in various types and generally circulate around the body to facilitate warding off pathogenic invaders such as bacteria or viruses, as well as cells turned cancerous. They mainly circulate throughout the vasculature including capillary beds, bone marrow, and lymph vessels. The five major types of WBCs are neutrophils, eosinophils, basophils, monocytes, and lymphocytes. There exists leukocytes that do not circulate but instead remain in a particular tissue. These include histiocytes and dendritic cells. They typically range in size from 8 to 18 µm in diameter depending on cell type and stage in development. Leukocytes make up roughly 1% of the total blood cells in the average human body. Leukocytes maintain the expression of CD47 and CD45 biomarkers which indicate to other cells what they are and that they should not be destroyed. Cells like dendritic cells are involved in the innate immune system, whereas cells like lymphocytes are part of the active immune system.
Neutrophils
Through the mechanism of chemotaxis, neutrophils are typically found migrating toward sites of inflammation that are secreting heightened concentrations of inflammatory chemical signals. Once they arrived at the site of inflammation, they release cytokines to activate other types of leukocytes. The distinct chemotaxis behavior of neutrophils allows for localized targeting of cancer sites using manipulated neutrophils. Neutrophils are the first to fend off pathogens and achieve such through phagocytosis, degranulation, and extracellular traps.
Eosinophils
Eosinophils are weaker than neutrophils at performing phagocytosis and effectively diminishing infectious pathogen populations. However, they excel at targeting and eliminating certain parasitic organisms through release of granules containing toxic proteins, including RNAases which are effective against viruses.
Basophils
Primarily involved in allergic reactions, basophils release granules containing heparin, histamine, and proteolytic enzymes. They possess similar anti-parasitic properties to eosinophils, as well as exhibit regulatory functions of T-cells and control the degree to which other immune cells are activated.
Monocytes
Once monocytes enter the region containing pathogens, they differentiate into macrophages that eliminate certain pathogens through phagocytosis. They serve a key role in presenting antigens to T-cells which produce immune system alerting signals upon coming into contact with said antigens.
Lymphocytes
Lymphocytes can be further divided into three main types. These include B-cells, T-cells, and natural killer (NK) cells. B-cells become activated and produce antibodies to bind and tag unwanted antigens for destruction and digestion. Once activated, they immediately begin producing antibodies for urgent action, or they circulate around the body as memory B cells to serve as protection against a particular antigen for long periods of time. T-cells have several key functions, including activation of other cells such as B-cells, helper T-cells and CD4+ cells, as well as elimination of virally infected cells and cancer cells. NK cells are involved in the innate immune system, and they kill pathogens via release of perforin and granzyme to directly destroy cell membranes, release of cytokines such as TNF-α to boost activity of other WBCs, as well as secretion of signals that trigger apoptosis. NK cells also can act to destroy pathogens without prior stimulation, unlike T-Cells.