"Eat me" imaging and therapy

Abstract

Clearance of apoptotic debris is a vital role of the innate immune system. Drawing upon principles of apoptotic clearance, convenient delivery vehicles including intrinsic anti-inflammatory characteristics and specificity to immune cells can be engineered to aid in drug delivery. In this article, we examine the use of phosphatidylserine (PtdSer), the well-known "eat-me" signal, in nanoparticle-based therapeutics making them highly desirable "meals" for phagocytic immune cells. Use of PtdSer facilitates engulfment of nanoparticles allowing for imaging and therapy in various pathologies and may result in immunomodulation. Furthermore, we discuss the targeting of the macrophages and other cells at sites of inflammation in disease. A thorough understanding of the immunobiology of "eat-me" signals is requisite for the successful application of "eat-me"-bearing materials in biomedical applications.

Keywords: Drug delivery; Imaging; Immune response; Leukocytes; Liposomes; Phagocytes; Phosphatidylserine.

Fig. 1

Systemic and local anti-inflammatory effects of PtdSer-based carriers. a) PtdSer-liposomes (PSL) exhibit systemic anti-inflammatory actions by means of inhibition of antigen presentation by dendritic cells (and possibly monocytes/macrophages) and inhibit T-lymphocyte proliferation in Th1 immune response. This is believed to be dependent on levels of transforming growth factor beta-1 (TGF-β1). Whether PSL directly modulate the function of dendritic cells in this process is not clear. b) PSL acted in various phagocytic and non-phagocytic cell types and elicited anti-inflammatory response. Some specific effects were also noted as indicated.