May 24th, 2012 by Michael Ricciardi
Despite many recent and remarkable successes in the field of biomedicine using nanotechnology to image, detect, treat and even cure diseases like cancer (in mice and humans), there have been lingering doubts among health professionals as to the safety of using nanoparticles (such as nanodiamonds) in medical applications.
To be sure, some earlier experiments with these tiny particles (measured in billionths of a meter) showed signs of cellular toxicity. (There is also some evidence that certain nanoparticles can damage plant DNA).
But in a recent, pioneering study using tiny luminescent crystals called ‘quantum dots’ in living primates, the metallo-crystalline dots were found to be safe over a one-year period following their introduction into rhesus monkeys.
The rhesus (macaque) monkeys were injected with cadmium-selenide quantum dots and remained in normal health over a 90-day period of observation and testing. Biological indicators (such as blood, respiration and weight) stayed in normal ranges. The primates’ major organs showed no abnormalities or pathologies.
Additionally, two of the monkeys were monitored for a year with neither exhibiting any sign of illness.
Co-researcher and paper coauthor Paras Prasad*, University of Buffalo professor of chemistry and medicine, stated in a press release:
“This is the first study that uses primates as animal models for in vivo studies with quantum dots. So far, such toxicity studies have focused only on mice and rats, but humans are very different from mice. More studies using animal models that are closer to humans are necessary.”
The crystalline quantum dots are useful to surgeons because they glow brightly in different colors (depending upon their atomic structure and size) and offer valuable applications in image-guided surgery and light-activated therapies, as well as highly sensitive diagnostic tests.
The particular type of quantum dots used in this study– cadmium selenide quantum dots — are among the brightest of such crystals and the most studied with applications beyond bio-imaging, such as in solar cell construction, LEDs, and even quantum computing.
As always, the researchers caution that more research is needed to ascertain the long-term effects of the nanocrystals in primates. They note that although no adverse side-effects or illnesses were found in the live animal ‘models’, analysis of the monkeys’ livers, spleens, and kidneys showed most of the potentially toxic cadmium remained in the organ tissues over the 90-day study period. Thus, the breakdown and ‘clearance’ of the nanocrystals from tissue is relatively slow.
Quoting from the paper abstract:
“…we show in a pilot study that rhesus macaques injected with phospholipid micelle-encapsulated CdSe/CdS/ZnS quantum dots do not exhibit evidence of toxicity. Blood and biochemical markers remained within normal ranges following treatment, and histology of major organs after 90 days showed no abnormalities. Our results show that acute toxicity of these quantum dots in vivo can be minimal. However, chemical analysis revealed that most of the initial dose of cadmium remained in the liver, spleen and kidneys after 90 days. This means that the breakdown and clearance of quantum dots is quite slow, suggesting that longer-term studies will be required to determine the ultimate fate of these heavy metals and the impact of their persistence in primates.”
Further, some in vivo experiments in mice showed that the “bioconjugated quantum dots were distributed in lymph nodes, kidneys, liver, lung, bone marrow and spleen” (Schipper et al, Al-Jamal et al, quote source: cited paper, below) and possibly remained in these organs/tissues for weeks or perhaps months (Fitzpatrick et al, Derfus et al).
This result is enough to warrant caution among many researchers, supporting those who advocate limiting the use of these crystals in biomedical applications — such as only using them in low dosages for image-guided surgical procedures (tumor discovery, etc.).
However, several earlier studies on quantum dot toxicity have shown that coating the cadmium-based core with another compound, such as ZnS, or adding a protective polymer coating, can reduce or eliminate toxicity in vitro and in vivo (Derfus et al).
The first-of-its-kind study was a collaborative effort between researchers at the University of Buffalo, NY, the Chinese PLA General Hospital, China’s ChangChun University of Science and Technology, and Singapore’s Nanyang Technological University.
Results of the research (A pilot study in non-human primates shows no adverse response to intravenous injection of quantum dots) were published May 20 in Nature Nanotechnology online. Research team members were: Ling Ye, Ken-Tye Yong, Liwei Liu, Indrajit Roy, Rui Hu, Jing Zhu, Hongxing Cai, Wing-Cheung Law, Jianwei Liu, Kai Wang, Jing Liu,Yaqian Liu, Yazhuo Hu,Xihe Zhang, Mark T. Swihart & Paras N. Prasad
*University of Buffalo’s Institute for Lasers, Photonics and Biophotonics (ILPB)
Second Image: (colloidal quantum dots) Walkman16 ; CC – BY – SA 3.0
Bottom Image: (quantum dot animation) Saumitra R Mehrotra & Gerhard Klimeck; http://nanohub.org/resources/8805
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