Nanomedicine, Volume I: Basic Capabilities
© 1999 Robert A. Freitas Jr. All Rights Reserved.
Robert A. Freitas Jr., Nanomedicine, Volume I: Basic Capabilities, Landes Bioscience, Georgetown, TX, 1999
184.108.40.206 Cytovehicle Selection
Which motile human cells may be the most appropriate cytovehicles? Since almost all cells exhibit migratory behavior at the embryonic stages of development, in theory all cells can probably be mobilized, given access to the nuclear chromatin and the ability to manipulate it (Chapter 20). However, it is a safer and simpler matter to choose cells which are exclusively or at least facultatively motile in the human adult. The obvious candidates include white cells (e.g., neutrophils, monocytes, dendritic cells, eosinophils, basophils), lymphocytes (up to ~0.5 microns/sec848), macrophages, and fibroblasts -- the speediest and most widely distributed cytovehicles -- as well as Kupffer cells, osteoblasts and osteoclasts, endothelial cells, smooth muscle cells, sperm cells, malignant tumor cells (after safing), neuronal cells, and some migratory epithelial (e.g., Langerhans' cells) and mesenchymal cells. Motions analogous to crawling transform blood platelets from smooth disks into spiny spheres to plug vascular leaks after injury.1564 Most bacteria are too small for whole-device entry, although their motility could be controlled by spoofing the external chemosensors, perhaps making them useful for piggybacking or towing (Section 220.127.116.11), or for steering to disposal sites. Other possibilities include parasites such as Entamoeba histolytica (found in the gut during amoebic dysentery, the liver during hepatic amebiasis, the bloodstream, and elsewhere), Giardia lamblia (an intestinal parasite), Plasmodium (a bloodstream parasite producing malaria), and so forth.
Erythrocytes are a special case. Though not motile, red blood cells are plentiful in the body, flow to within ~50 microns of virtually every tissue cell in the body, and have a tough, floppy outer plasma membrane. Experimentalists often replace the hemoglobin solution of red cells with an isotonic aqueous solution, producing "ghost cells" that mechanically behave much like the original cells minus the respiratory functions. In theory, nanorobots could enter an erythrocyte ghost cell and erect an artificial internal cytoskeleton to control cell shape, rotation, and possibly simulate amoeboid motions. However, naturally motile cells such as white cells already possess hardwired programs for creeping, diapedesis, object engulfment, etc. that can be triggered mechanically or biochemically with a minimum of effort (Section 18.104.22.168), hence these cells are much more attractive cytovehicles.
Passive cytocarriage is widely practiced in the microscopic world. Dengue-2 virus enters macrophages and B lymphocytes, hitching a ride;3082 bacteria stably associated with human cells (e.g., E. coli in the intestinal mucosa) are well known. Larger microbes such as the tuberculosis bacterium also employ opportunistic cytocarriage.1558 These bacteria are specially adapted to recognize and lock on to the large macrophages distributed throughout pulmonary tissue, and then to induce these cells to ingest them. Once inside the macrophages, the microbes get a free ride into the blood or the lymphatic system, enabling them to reach destinations all over the human body.384
Last updated on 21 February 2003