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

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

15.4.3.2.1 Phagocytosis and Opsonization in Blood

The first critical event that occurs upon injection of a particle into the bloodstream is the rapid and efficient process of conditioning through the interaction of plasma proteins with the particle surface [2904]. The rate and extent of particle uptake and the nature of the conditioning material depend both on particle size and on the nature of the particle itself [2905, 2906]. Hydrophobic particles such as unmodified pure diamond may become coated with a variety of blood components (Sections 15.2.2 and 15.3.1.1) in a process known as “opsonization.” This renders the particles more recognizable by phagocytes within the blood compartment, and particularly by the macrophages in the liver (Kupffer cells; Section 15.4.3.2.3) and in the spleen (Section 15.4.3.2.4). Opsonization also may promote particle (e.g., nanorobot) aggregation.

Important opsonic materials can include complement [2907] (Section 15.2.3.2) and immunoglobulins (Section 15.2.3.3). Organ-specific opsonins for liver and spleen macrophages have been found [2908]. However, if particles are hydrophilic and present a steric stabilizing barrier to the external environment, the extent of particle conditioning can be minimized and altered (Section 15.2.2). For example, it is well established that certain surfaces can encourage the uptake of dysopsonic factors that will render the particle less recognizable by resident macrophages [2886, 2909, 2910]. Opsonic and dysopsonic processes are dynamic in nature with a competition for the surface and continuous phases of uptake and displacement. Albumin is often the first component to be adsorbed because it is the most abundant blood protein. Other components are present at lower concentrations but higher affinity for the surface, and compete for adsorption subsequently (Section 15.2.2.1). Note however that macrophages can bind and engulf some particles even in the absence of specific opsonins [2911].

Medical nanorobots should attempt to avoid being unintentionally phagocytosed by neutrophils and monocytes in the circulation, prior to extravasation or transformation of these cells in response to chemotactic signals from injured tissues. For example, one experiment studied the phagocytosis of three types of 1.5-micron polymeric particles with different surface wettabilities that were incubated with blood taken prior to a cardiopulmonary bypass procedure [2906]. One of the three particle types, PMMA, adhered well to phagocytes and was readily ingested (14 particles/monocyte and 11 particles per neutrophil), whereas the other two particle types, MMA/HEMA and PMMA/PVAL, showed almost no adhesion or phagocytosis – although after the bypass procedure the leukocytes evidently became activated and could then phagocytose all particle types [2906]. Stealth liposomes (Section 15.2.2.1) also show a marked decrease in phagocytosis by macrophages [5281].

Last updated on 30 April 2004