Jun 8, 2012
Functionalized nanocrystals image tumours
Researchers at the University of Hamburg in Germany have made new contrast agents for tumour imaging based on functionalized semiconductor quantum dots and iron oxide nanocrystals. An added plus is that the nanoparticles are non-toxic, even at very high concentrations (ACS Nano 6 3346).
Fluorescent semiconducting quantum dots and superparamagnetic iron oxide nanocrystals can be used for in vivo and in vitro medical imaging but the particles need to be made water soluble and stable in biological environments first. One way to do this is to attach ligands to the nanoparticles, but the attachment processes have proved to be more difficult than first imagined. Typical problems include insufficient binding of the water-soluble nanoparticle ligands under biological conditions, that is, in highly salty solutions and in the presence of serum proteins, for example. These proteins may either bind to the outermost ligand shells or even substitute for the particle ligands themselves.
Now, Horst Weller and colleagues have proposed a new ligand system based on the amphiphilic polymer polyisoprene-block-poly(ethylene oxide). The biofunctionalization technique consists of four steps: the first and second steps involve activating the surface of CdSe/CdS/Zns quantum dots with a pre-coating, which then acts as a nucleation point for subsequent encapsulation of the nanoparticles by the polymer. The polymer forms a protecting hydrophobic shell around the nanoparticles.
The third step consists of additional crosslinking of the hydrophobic shells, which substantially increases the stability of the nanoparticles in a wide range of biological environments. The final step is the covalent coupling of "recognition" molecules, such as antigens – in this case one that interacts with the antibody T84.1.
The conjugated quantum-iron oxide nanocrystals can be used to image tumours because the coupled antibodies recognize the tumours and specifically bind to them, explains Weller. The encapsulated nanoparticles either fluoresce or show a strong MRI signal that can easily be detected.
"Our method is very general," he told our sister site nanotechweb.org, "because it allows many different nanoparticles or pharmaceuticals to be incorporated into the capsules. What is more, the surface chemistry also allows coupling of a variety of different biologically active molecules."
The team tested its technique on mice with skin tumours by injecting a solution containing the T84.1-coupled and functionalized nanoparticles into the animals. Magnetic resonance imaging just three hours after injection showed that the tumours had significantly decreased in size, with the result becoming even more pronounced 12 and 24 hours afterwards. According to the researchers, the results show that the nanoparticles had specifically bound to the tumours.
"One of the goals of nanomedicine is to produce functionalized nanoparticles that recognize specific target cells, such as cancer cells," explained Weller. "The way we encapsulate nanoparticles with precisely optimized block-copolymers fulfils this requirement much better than many commercial particles, while allowing for a large variety of bioconjugation techniques for recognition molecule coupling."
About the author
Belle Dumé is contributing editor at nanotechweb.org.