Criteria set for quantum dot clinical safety
Nanomedicine
January 2, 2008
Functionalized quantum dots (QDs) offer considerable potential for targeted disease detection and treatment. However, the clinical feasibility of such therapies requires the QD carriers to be removed intact from the body or to biodegrade into biologically benign components.
Failure to meet these conditions could lead to unacceptable toxicity or interference with subsequent medical imaging scans.
A team from Beth Israel Deaconess Medical Center and Massachusetts Institute of Technology has now defined key criteria that inorganic, metal-containing QDs need to meet if they are to be cleared by urinary excretion [Choi et al., Nat. Biotech., doi: 10.1038/nbt1340].
Hak Soo Choi and colleagues first investigated how differently charged organic coatings affect the overall size of metal-containing QDs, a factor that limits their passage through the kidneys.
Fluorescent CdSe/ZnS QDs were coated with dihydrolipoic acid (DHLA; anionic coating), cysteamine (cationic), cysteine (zwitterionic), or DHLA-connected polyethylene glycol (DHLA-PEG; neutral) and incubated with serum proteins.
Purely anionic and cationic coatings promote serum absorption and lead to an increase in hydrodynamic diameter of >15 nm. Conversely, a zwitterionic coating produces the highest solubility and the lowest hydrodynamic diameter (<~10 nm).
The team then tagged cysteine-coated particles of varying sizes with a gamma-ray emitting isotope (99mTc). Radiolabeled particles with hydrodynamic diameters ranging from 4.36 nm to 8.65 nm were mixed with saline and injected into rats.
In vivo fluorescence imaging and radioactive measurements were used to assess the link between urinary excretion and particle size.
The team conclude that, for clinical use, the hydrodynamic diameter of nonbiodegradable metal QDs should be <5.5 nm. There may be additional criteria too.
“The ability of nanoparticles to pass the kidney filters is a function of their shape, size and surface charge,” says Choi. “We are investigating the effect of mass and charge on the biodistribution and metabolism using various shapes of molecules.”
Paula Gould