Nanomedicine, Volume IIA: Biocompatibility
© 2003 Robert A. Freitas Jr. All Rights Reserved.
Robert A. Freitas Jr., Nanomedicine, Volume IIA: Biocompatibility, Landes Bioscience, Georgetown, TX, 2003
126.96.36.199 Biocompatibility of Metals, Semiconductors, and Quantum Dots
Noble metals [2282-2286] such as gold, platinum [5685-5687], and palladium are very biocompatible, silver [2360-2363] (including nanocrystalline silver [6207-6210]) is moderately biocompatible, and titanium is widely used in implants and surgical staples (Section 188.8.131.52). The biocompatibility of metals and metal leachates is particularly well-studied [2022, 6030-6033]. Titanium shows excellent biocompatibility [280-282, 1423, 5695-5710, 6053] and is apparently well tolerated after implantation for at least up to 13 years , as is, more specifically, titanium dioxide or titania [5700, 6153-6164] – although a U.S. Army study found slightly higher toxicity with TiO2 ultrafine smoke particles than with larger particles , and TiO2 nanoparticles used in sunscreens apparently catalyze the photooxidation of organics with hydroxyl radical formation [6184-6186] with at least one group  reporting (and still a matter of ongoing dispute [6186, 6187]) sunlight-illuminated titania nanopowder catalyzing DNA damage both in vitro and in some human cells. Single-crystal silicon is not as biocompatible  (the body will grow a protein sheath around it to isolate it [2287, 2288]), and phagocytosable hydrophilic silica crystal particles are highly membranolytic , cytotoxic , and produce crystal-induced inflammation . But porous single-crystal silicon provides better mechanical anchorage for cells and thus is more biocompatible than nonporous silicon . Porous silicon can support the ingrowth of the natural mineral hydroxyapatite, the chief structural component of human bone, without producing an isolation sheath . Silicon nitride also appears to have good biocompatibility . Fluoride-ion surface-implanted titanium has antibacterial properties but does not inhibit the proliferation of fibroblast L929 cells .
Luminescent semiconductor quantum dots  and other nanoparticles have been covalently coupled to biorecognition molecules and used in ultrasensitive biological detection [5246-5253, 5639, 5741-5745] or drug delivery . These nanometer-sized conjugates are said to be water-soluble and biocompatible , and it is true that a few micron3/cell of engineered nanoparticles are tolerated by living cells when employed as intracellular fluorescent reporters . However, these nanoparticles often contain arsenic- or cadmium-based compounds [5248-5250]. These are potentially highly toxic metals  if solubilized or eluted from the nanoparticles into the cytosol or extracellular fluids. Other approaches, such as PEBBLE (Probes Encapsulated By Biologically Localized Embedding) sensors , are nanoscale spherical devices consisting of sensor molecules trapped in a chemically inert protective matrix which allows dyes to be used for intracellular sensing that would normally be cytotoxic; Halas group’s “nanoshells” are also being investigated as sensors and for drug delivery [5746, 6066-6068]. Thorough toxicological , environmental [5748, 5749], and biocompatibility [5638, 5742, 5750] studies of these materials have not yet been undertaken but would be well advised.
Ruoslahti and coworkers  have developed hybrid organic/inorganic molecules consisting of nanocrystalline semiconductor particles (<10 nm ZnS-capped CdSe quantum dots) coated with peptide segments (“homing peptides” much smaller than antibodies) that target specific vascular addresses [5751-5756] inside the bloodstream and living tissues, for example, lymphatic vessels in tumors . The nanoparticles reportedly produce no blood clotting , and the addition of polyethylene glycol to the coating prevents nonselective accumulation in reticuloendothelial tissues . Notes Ruoslahti: “These results encourage the construction of more complex nanostructures with capabilities such as disease sensing and drug delivery.” And fluorescent semiconductor nanocrystals individually encapsulated in phospholipid block-copolymer micelles were nontoxic (at <5 x 109 nanocrystals per cell) when injected into Xenopus embryos by Dubertret et al .
Timp’s group at the University of Illinois  is experimenting with 7-micron silicon-based microchips inserted into living cells to verify cell viability, as a precursor to testing GHz-frequency rf microtransponders using nanotube antennas inside cells.
Last updated on 30 April 2004