Aptamers, short stretches of DNA or RNA that can act much like antibodies, have shown promise as targeting agents for selective nanoparticle trafficking to tumors.
Their ability to recognize and bind to tumor-specific molecules is undisputed, but the strength with which aptamers bind to their molecular targets is often insufficient to act as an effective targeting agent under clinically relevant conditions.
Now, a research team headed by Weihong Tan, Ph.D., at the University of Florida has shown that adding up to 80 aptamers on a single gold/silver nanorod increases the binding ability of this construct by at least 26-fold compared with that of an individual aptamer. Using dye-labeled aptamers, the investigators also were able to produce a cancer-detecting probe whose fluorescent signal is more than 300 times greater than that produced by individual dye-labeled aptamers. This work was published in the journal Analytical Chemistry.
In earlier work, Tan and his colleagues had shown that aptamer-labeled magnetic nanoparticles could be used to separate cancer cells from a mixture of normal and malignant cells. In the current study, he and his colleagues have extended the utility of aptamer targeting by demonstrating that multiple copies of an aptamer, when distributed along the surface of a nanorod, dramatically increase the binding affinity of the nanoscale construct through cooperative binding.
Cooperative binding works in much the same way as the multiple hooks and loops on Velcro®. If the interaction between one hook and loop, or one aptamer and its cellular target, is disrupted, other binding pairs maintain the connection between the two objects, whether it be the nanorod and cancerous cell or the two halves of a Velcro® pair. These findings, the investigators note, suggest that even aptamers that bind weakly, but specifically, to a cancer-related target could still prove useful as nanoparticle targeting agents. Indeed, the use of multiple weak-binding aptamers could reduce nonspecific binding of targeted nanoparticles or nanorods to healthy cells.
This work, which was supported in part by the NCI, is detailed in the paper “Cancer cell targeting using multiple aptamers conjugated on nanorods.” An investigator from National Taiwan University in Taipei, Taiwan, also participated in this study. An abstract of this paper is available through PubMed.