Quantum clearance

The paper:

H.S. Choi et al., "Renal clearance of quantum dots," Nat Biotech, 25:1165–70. (Cited in 74 papers)

The finding:

Hak Soo Choi and John Frangioni of the Beth Israel Deaconess Medical Center in Boston, Mass., wanted to maximize the safety profile of quantum dots—nanoscale semiconductor particles loaded with toxic heavy metals. The researchers injected mice with quantum dots ranging from 1 to 20 nm in diameter and showed that the animals could get rid of dots smaller than 5.5 nm through the kidneys, but larger particles accumulated in the spleen, liver, and lungs.

The impact:

"All the bio-applications of nanotechnology have some problems because of safety issues," says Hitasaka Kobayashi, an imaging scientist at the National Cancer Institute in Bethesda, Md., who was not involved in the research. Thus, this study helped define guidelines that other researchers can now use to minimize the toxicity of nano-sized particles, he notes.

The follow-ups:

Kobayashi showed that similar-size constraints determine clearance of branched, star-shaped nanoparticles called dendrimers (Nanomedicine 3:703–17, 2008). Sanjiv Gambhir of Stanford University also measured clearance rates of quantum dots as a function of coating material, size, and length of polymer chain attachments on the outside of the particles (Small, 5:126–34, 2009).

The target:

Choi has unpublished work showing that 70% of his quantum dots can successfully target tumors, whereas earlier reports got at most 10% of the dots to the location of interest. That could boost the effectiveness of quantum dots in cancer treatments and prevent unintended side effects, he says.

Particle Diameter	% in the liver	% in the lungs	% in the spleen
4.36 nm	4.5	<1	<1
8.65 nm	26.5	9.1	6.3

What the authors have shown is a good first step. What matters at the end is whether these QD nanodelivery of drug/gene/RNAi etc. reaches the target, does its job efficiently, and then comes out without producing adverse effects or, at worst, produces manageable side effects. Sorry to say this, but there has been far too much hype before. One simply has to read the headlines that appeared after RNAi discovery.

The localization of the larger particles within the liver primarily, followed by the spleen and lungs to a lesser extent, are the classically typical profile of clearance by the reticuloendothelial system. The scientists need to bone-up on that area of basic physiology to assure that the particles go where they therapeutically need to go rather than be cleared from the blood within minutes to those organ-specific, specialized macrophages where they will do no good.