Drug smuggling microparticles play dress-up

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Science Translational Medicine  01 Aug 2018:
Vol. 10, Issue 452, eaau7382
DOI: 10.1126/scitranslmed.aau7382


Hemolysate coating prolongs circulation of red blood cell–shaped microparticles.

The body’s defense mechanisms keep us healthy by removing foreign particles and invaders but can also complicate medical interventions by interfering with therapeutic agents. A recent report by Hayashi et al. describes a method of protecting such agents from overzealous immune response through performing a feat of cellular dress-up that may be able to fool even the most vigilant immune cells.

Microparticles that mimic the biconcave discoidal shape of red blood cells avoid in vivo clearance caused by occlusion in lung capillaries and filtration by the spleen. Hayashi and co-workers previously electrospun cellulose derivatives into red blood cell (RBC) shape–mimicking microparticles that proved to be proficient smugglers, capable of delivering transforming growth factor–β to the liver and pilfering cortisol from their surroundings. Although these microparticles had favorable organ distribution profiles, they were susceptible to clearance by immune cells. In the recent report, the group improved their RBC-shaped microparticles by sonicating them with the debris of lysed mouse blood cells. This process coated microparticles with blood cell membranes, resulting in the particles gaining an average of 350 nm in diameter and camouflaging them from immune attack. Coated microparticles maintained approximately fourfold higher concentrations in tail vasculature of mice versus uncoated RBC-shaped particles 24 hours after injection. The ability of lysate coating to render particle surface charges more similar to that of native RBCs was hypothesized as an explanation for its capability to prolong circulation time. Furthermore, coated microparticles displayed CD47 protein, a “don’t eat me” marker present on the surface of RBCs that inhibits their clearance by macrophages.

Further studies need to be conducted to determine if the lysate coating altered the biodistribution of the microparticles or hindered their ability to sequester and release desired compounds. However, this work is a reminder that as we engineer increasingly sophisticated in vivo constructs, we shouldn’t overlook form and feel because our bodies might care about aesthetics, too.

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