Quantum Dots: Heralding a Brighter Future for Clinical Diagnostics

Tamer M Samir; Mai MH Mansour; Steven C Kazmierczak; Hassan ME Azzazy


Nanomedicine. 2012;7(11):1755-1769. 

In This Article

Toxicity Issues

In spite of all their advantages and potential, the use of QDs for in vivo applications may be hindered by concerns over their potential cytotoxicity due to their semiconductor components and some coating chemicals. Even for in vitro applications, there is concern over the disposal of QDs into the environment. The main concern is the robustness of the surface coating, as the CdSe core of the QD could be exposed to UV damage or air oxidation if the surface coating is unstable. Consequently, the toxic Cd ions would be released from the QD core. The ZnS capping would protect the core from air oxidation, but not from UV damage. There are also concerns about toxicity related to the molecules used for surface functionalization of the QDs. Coating of QDs with PEG or encapsulation in micelles may help them to resist UV damage.[4,60,61] CdTe QDs lacking a protective shell or surface coating have been shown to generate cytotoxic reactive oxygen species when incubated with live cells.[35] As for silicon QDs, despite the fact that their synthesis is slightly more challenging with regards to their water dispersion, they are quite appealing on the toxicity front. They have been used for cancer imaging and tested on mammalian cell lines, and have been found nontoxic at concentrations needed for biological imaging.[52,62] ZnO QDs are generally considered to be environmentally friendly and they have also been found to be nontoxic to mammalian cells in vitro even at the high concentration of 100 µg/ml. This work demonstrated their superior resistance to photobleaching and tolerance for UV irradiation, compared with CdSe/ZnS, which is a contributor to QDs' toxicity.[59]

Several studies using live cell/animal models found QDs to be nontoxic for periods up to several months.[60] In addition, properly capped CdSe/ZnS QDs with a hydrophilic coating showed no adverse effects on cells in proliferation studies.[3,6,7] However, these finding are not conclusive. For instance, at higher concentrations of QDs, beyond 5 × 109 QDs per cell, Xenopus embryo development was affected.[3,14]

Several factors affect the toxicity of QDs including size, surface charge, route and duration of exposure, dosage, and local environmental conditions such as pH.[33,35,60] The risks of exposure through the skin and ingestion are unknown. In addition, little is known about the metabolism or excretion of QDs.[60] Functionalized QDs larger than 10 nm are too large to be excreted by glomerular filtration and are more likely to accumulate in the body.[33] Extensive investigations of QD toxicity and clearance mechanisms are warranted to guide their utility for medical applications.