Monocyte-mediated drug delivery systems for diagnosis and therapy

The mononuclear phagocytic system (MPS) is a part of the immune system that consists of phagocytic cells, primarily monocytes and macrophages. Both circulating monocytes and neutrophils phagocyte debris, and foreign particles in the blood including particulate drug delivery systems. Inflammation characterizes several pathological disorders including cardiovascular disorders and cancer, and the inflammatory cascade involves significant infiltration of phagocytic cells. Additionally, the brain is under immunological surveillance, allowing monocytes and neutrophils to cross the BBB. The propensity of monocytes for rapid phagocytosis of particulate matter provides a rational approach for delivering drugs in inflammatory-associated disorders.

In this presentation we will review therapeutic as well as diagnostic approaches mediated via specific nanoparticles (NP), which are avidly uptaken by circulating monocytes. The partial and transient depletion of circulating monocytes by liposomes or polymeric NP, containing bisphosphonate and other drugs, results in the prevention of restenosis (now in phase IIb clinical studies).

Modulation of monocytes sub-populations by NP favorably affects heart function in the rat myocardial infarction model. The mechanism of immunomodulation was elucidated by dissecting the effects on monocytes subsets (‘pro’/‘anti’-inflammatory), in animal models of cardiovascular disorders.

Monocytes can serve as a courier of specific NP to the CNS, bypassing the blood-brain barrier (BBB) without affecting it, effectively transporting drugs that are brain- impermeable.

Finally, when the cargo is non-cytotoxic to the cell carrier, nano-size liposomes can be targeted to inflamed regions for diagnostic purposes. Liposomal delivery of quantum dots (QDs) enables an efficient fluorescent signal with no toxicity, in animal models of cardiovascular disorders and cancer.