© 2003 Robert A. Freitas Jr. All Rights Reserved.

Robert A. Freitas Jr., Nanomedicine, Volume IIA: Biocompatibility, Landes Bioscience, Georgetown, TX, 2003

15.4.3.2 Phagocytosis of Bloodborne Microparticles

Measurement of the phagocytic capacity (ingestible particle volume) of an animal’s RES is traditionally accomplished by determining the rate of disappearance of stable, inert, uniform particles such as gelatin-stabilized carbon particles. Upon intravenous injection of such particles, about 90% are taken up by the liver, most of the remainder by the spleen [2888]. One-micron diameter fluorescent beads administered IV to rats are preferentially cleared by the spleen, liver, and lungs [2889] through a complex interaction of geometric and phagocytic influences. Another experiment with amino-modified 0.1- to 1-micron polystyrene particles in mice found that blood elimination half-life ranged from 80-300 seconds [2890]. Aside from purely geometric considerations (Section 15.4.2), once inert medical nanorobots have been opsonized (Section 15.4.3.2.1) they may subsequently be phagocytized by phagocytes resident most importantly in the liver (Section 15.4.3.2.3) and spleen (Section 15.4.3.2.4), and also in some cases in the lung (Section 15.4.3.2.2) and kidney (Section 15.4.3.2.5).

The smallest particles <0.1 micron in diameter (e.g., 30-100 nm technetium particles [2891]) that remain in circulation distribute primarily to the bone marrow [2891, 2892],* where mononuclear phagocytes [2893-2897] and phagocytic bone marrow fibroblasts [2898] have been shown to ingest various particles such as polystyrene microspheres [2898] and polyacrylamide microparticles [2893]. Microspheres and lipid nanoparticles are also frequently employed to carry antitumor agents into tumors [2491, 2900, 2901]. For instance, cationic magnetic aminodextran microspheres 1-2 microns in diameter preferentially accumulate in brain tumors as compared to neutral magnetic dextran microspheres [2902].

* Interestingly, in one experiment [2899], carbon-particle laden bone marrow macrophages in chickens migrated from the erythropoietic sinus through the sinus wall to the extravascular area (the granulopoietic region) 1-3 days post-injection. After 7 days almost all the carbon-laden macrophages accumulated in macrophage islets mainly around the lymphatic nodules in the extravascular area [2899].

The ultimate fate of inert microparticles phagocytized from the blood varies but may involve transport into specific organs, the lymphatic flow (Section 15.4.3.4) or the cerebrospinal flow [2903], or may involve granulomatogenesis in situ (Section 15.4.3.5).

Last updated on 30 April 2004