So-called “theranostic” nanoparticles are capable of providing both a diagnostic as well as a therapeutic function in the same nanoparticle. Such theranostic nanoparticles have been primarily developed to address cancer diagnosis and treatment.
Now researchers at Singapore’s A*STAR Institute of Materials Research and Engineering and colleagues at the National University of Singapore have developed a theranostic nanoparticle that has the added benefit of being able to offer two distinct cancer therapies.
"This is the first nanoplatform that can offer on-demand and imaging-guided photodynamic therapy and chemotherapy with triggered drug release through one light switch," said Bin Liu of A*Star in a news release.
At the center of the new system is a nanoparticle made from a polyethylene-glycol-based polymer that carries a small peptide component that allows it to bind preferentially to specific cell types. In addition, the polymer-based nanoparticle also carries the chemotherapy drug doxorubicin. The polymer also can be stimulated by light to release reactive oxygen species (ROS), which are chemically reactive molecules containing oxygen.
Surface peptides (purple arrows) allow fluorescent nanoparticles to bind to a protein (green) on the target cells and be taken up into the cells. Light exposure prompts the nanoparticles to generate reactive oxygen species (ROS), kills the cells, and also liberates the drug doxorubicin (orange), which can then enter the cell nucleus.A*STAR Institute of Materials Research and Engineering/Wiley-VCH
While ROS can sometimes produce a negative effect in the body when an excessive amount of an ROS called superoxide (SO) is released into the blood after brain injuries, in this case the ROS generated by the light stimulation has a direct photodynamic therapeutic activity, which destroys the targeted cells.
The polymer also has a natural fluorescence that can help identify where the cancer cells have accumulated.
In research, which was published in the journal Angewandte Chemie International Edition, the researchers used the nanoparticle on a mixture of cultured cancer cells that had a surface protein that could bind to the targeting peptide in the nanoparticle. In the demonstration, when a light source was directed at the sample, the fluorescence of the nanoparticle indicated that the targeted cells had taken up the nanoparticle and that the ROS and doxorubicin had been released into the cells.
While the in vitro cancer cells could be effectively treated by the nanoparticle, inside a living body the issue becomes a bit more complicated.
"The white light used in this work does not penetrate tissue sufficiently for in vivo applications," Liu explains, "but we are now attempting to use near-infrared laser light to improve the tissue penetration and move toward on-demand cancer therapy."
Dexter Johnson is a contributing editor at IEEE Spectrum, with a focus on nanotechnology.