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

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

15.3.6.3 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 15.2.1.3). 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 [5823], 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 [6183], and TiO₂ nanoparticles used in sunscreens apparently catalyze the photooxidation of organics with hydroxyl radical formation [6184-6186] with at least one group [6184] 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 [569] (the body will grow a protein sheath around it to isolate it [2287, 2288]), and phagocytosable hydrophilic silica crystal particles are highly membranolytic [2330], cytotoxic [652], and produce crystal-induced inflammation [2323]. But porous single-crystal silicon provides better mechanical anchorage for cells and thus is more biocompatible than nonporous silicon [1769]. Porous silicon can support the ingrowth of the natural mineral hydroxyapatite, the chief structural component of human bone, without producing an isolation sheath [2288]. Silicon nitride also appears to have good biocompatibility [2518]. Fluoride-ion surface-implanted titanium has antibacterial properties but does not inhibit the proliferation of fibroblast L929 cells [4801].

Luminescent semiconductor quantum dots [5740] and other nanoparticles have been covalently coupled to biorecognition molecules and used in ultrasensitive biological detection [5246-5253, 5639, 5741-5745] or drug delivery [5746]. These nanometer-sized conjugates are said to be water-soluble and biocompatible [5253], and it is true that a few micron³/cell of engineered nanoparticles are tolerated by living cells when employed as intracellular fluorescent reporters [4238]. However, these nanoparticles often contain arsenic- or cadmium-based compounds [5248-5250]. These are potentially highly toxic metals [5254] 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 [4258], 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 [5747], 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 [5739] 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 [5739]. The nanoparticles reportedly produce no blood clotting [5757], and the addition of polyethylene glycol to the coating prevents nonselective accumulation in reticuloendothelial tissues [5739]. 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 [6027].

Timp’s group at the University of Illinois [6235] 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