Engineering Antiphagocytic Biomimetic Drug Carriers

Abstract

Drug-delivery carriers have the potential to not only treat but also diagnose many diseases; however, they still lack the complexity of natural-particulate systems. Cell-based therapies using tumor-targeting T cells and tumor-homing mesenchymal stem cells have given researchers a means to exploit the characteristics exhibited by innate-biological entities. Similarly, immune evasion by pathogens has inspired the development of natural polymers to cloak drug carriers. The ‘marker-of-self’ CD47 protein, which is found ubiquitously on mammalian cell surfaces, has been used for evading phagocyte clearance of drug carriers. This review will focus on the recent progress of drug carriers co-opting the tricks that cells in nature use to hide safely under the radar of the body’s innate immune system.

Co-coating of receptor-targeted drug nanocarriers with anti-phagocytic moieties enhances specific tissue uptake versus non-specific phagocytic clearance

“…In nature, the CD47 expressed on erythrocytes or other cells binds to SIRPα on phagocytic cells, and the resulting anti-phagocytic signal is “balanced” against pro-phagocytic signals, e.g., that resulting from opsonization molecules, oxidized markers, etc., interacting with FcR, scavenger receptors, etc. 20,28,29 The resulting balance can turn on or off the phagocytic process depending on the “weight” of these two opposed signals. 20,28,29 While non-targeted NCs coated with CD47 may inhibit phagocytosis, the presence on a NC surface of targeting antibodies, which can interact and induce endocytosis on their own may outweigh this property.…”

“…20,28,29 The resulting balance can turn on or off the phagocytic process depending on the “weight” of these two opposed signals. 20,28,29 While non-targeted NCs coated with CD47 may inhibit phagocytosis, the presence on a NC surface of targeting antibodies, which can interact and induce endocytosis on their own may outweigh this property. In particular, since macrophages express a basal level of ICAM-1 35 and binding of NCs to ICAM-1 induces endocytosis, 37 whether this pro-uptake signal or the CD47 anti-phagocytic signal would prevail was unknown.…”

“…In the context of drug delivery, 29 murine macrophage cell cultures incubated in the presence of soluble CD47 were observed to exert lower phagocytosis of colloidal drug carriers added thereafter. 30 In addition, either the ectodomain of CD47 or specific peptides derived from its SIRPα-binding region have been coupled to the surface of micro- or nano-devices, which has then been shown to reduce phagocytosis and clearance of said devices both in cell cultures and laboratory animals.…”

CD47 EnhancesIn VivoFunctionality of Artificial Antigen-Presenting Cells

“…Micro-meter sized aAPC display limited lymphatic drainage(21) and are cleared and phagocytosed by professional phagocytes such as macrophages and immature DC(22–24). Therefore, many efforts are made to generate optimal aAPC scaffolds that exhibit minimal systemic clearance and maximal in vivo functionality(11). …”

Antitumor Therapy Using Nanomaterial-Mediated Thermolysis

“…53 Hyaluronic acid is a naturally occurring polysaccharide expressed by Streptococci which has anti-phagocytic properties and its cognate receptor is upregulated on tumor cells. 54 Immunologically modified SWNTs were developed using glycated chitosan (GC) by Zhou et al 56 57 The synergy between immunological and photothermal effects of SWNT-GC was shown to increase cell destruction. Specifically, 980-nm laser light was used to induce cell destruction and also led to secretion of damage associated molecular pattern molecules (i.e., molecules which can perpetuate immune response).…”