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

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

15.4.3.6.8 Inhibit Phagocyte Metabolism

Medical nanorobots might find it useful to slow or temporarily inhibit phagocyte metabolism to improve the likelihood of avoidance or escape. The simplest method is to selectively absorb oxygen or glucose intracellularly (ideally after avoiding or escaping the phagolysosome), thus asphyxiating or starving the phagocyte. This assumes these substances are not sequestered in an intracellular microzone (Section 15.5.7.5) or membrane-enclosed compartment close to the metabolic machinery that is consuming them, and that these substances can be absorbed by the intracellular nanorobots faster than the maximum transport rate into the cell (Section 10.4.2.1). Alternatively, a coordinated population of extracellular nanorobots could temporarily and reversibly hypoxify or hypoglucosify the local environment as a macrophage approaches. Hypoxia inhibits macrophage migration [3571], probably due to metabolic changes in the cell.

Another method is to deny energy to the cell by selectively absorbing intracellular ATP using molecular sorting rotors on the nanorobot exterior (ideally after avoiding or escaping the phagolysosome). Again, this assumes the ATP is not sequestered in an intracellular microzone (Section 15.5.7.5) or membrane-enclosed compartment that is diffusion-inaccessible to the nanorobot, and that the ATP can be absorbed by the intracellular nanorobots faster than the maximum production rate of the intracellular mitochondrial population (Section 8.5.3.10). In nature, the adenylate cyclase bacterial exotoxins such as anthrax toxin edema factor [3368] and pertussis toxin [3369] act to depress phagocytic activity in a similar manner. For instance, Bordatella pertussis releases an extracellular adenylate cyclase which, when taken up by phagocytic cells, sabotages intracellular metabolism by converting internal ATP to cAMP, effectively de-energizing the cells [3369]. Yersinia similarly disarms macrophages using a hybrid YopT-adenylate cyclase [3572]. Depletion of extramitochondrial intracellular ATP pools converts apoptosis to necrosis in human T cells subjected to two classic apoptotic triggers [5934].

Dansylcadaverine, amantadine, and rimantadine have actions on phospholipid metabolism [3355] and reduce the production of membrane lipids such as phosphatidylcholine that are necessary for engulfment. Numerous phagocyte phospholipid and cholesterol synthesis inhibitors are known [3436]. Intracellular free oxygen, such as might be released by medical nanorobots from onboard tanks containing pressurized gases [3573], regulates enzymatic activity via enzyme activation or deactivation by S-thiolation controlled by local oxygen tension [3574]. Intracellular oxygen also impairs arachidonic acid metabolism [3575] and phagocytic function [3576-3579] in lung macrophages, and can have intracellular toxicity [3581, 3582]. Inhibition of natural antioxidants increases cellular susceptibility to oxygen toxicity [3580, 3581]; at the organismal level, O₂ exposures exceeding 2.5 atm can cause seizures in animals [3581].

Last updated on 30 April 2004