Efforts to create nanoparticles that deliver anticancer drugs or imaging agents to tumors while avoiding healthy cells are often stymied by a lack of known tumor targets, that is, molecules found on the surface of malignant cells but not healthy cells. While researchers continue to search for such tumor-specific markers, an international team of investigators has found a way of creating peptide-based targeting agents that do not require knowing in advance what the target is. This technique could have a profound, positive impact on the development of targeted nanoparticles for cancer imaging and treatment.
Reporting its work in the journal Molecular Cancer Research, a research team headed by Byung-Heon Lee, Ph.D., of the Kyungpook National University in Daegu, Korea, and Erkki Ruoslahti, M.D., Ph.D., of the Burnham Institute for Medical Research and a member of the Center of Nanotechnology for Treatment, Understanding, and Monitoring of Cancer CCNE, described its use of a technique known as phage display to create a large library of random peptides. They then screened these peptides to see if any were capable of binding to primary human bladder tumors, identifying six potential targeting agents. Of these six peptides, one nine-amino-acid peptide bound to bladder tumor tissue but not to healthy bladder tissue.
To test whether the peptide could target bladder tumors in an animal, the investigators first added a fluorescent molecule to the peptide and then injected it into rats with human bladder tumors. Using fluorescence microscopy, the researchers showed that this peptide targeted tumors specifically, with no fluorescence appearing in healthy tissue. The investigators then examined urine from humans, finding that the fluorescently labeled peptide bound to cells in urine from patients with bladder cancer. In contrast, the peptide did not bind to anything in urine from healthy individuals or from patients with bladder inflammation. The investigators note that they will now attempt to use this peptide to identify the bladder tumor-specific molecule to which it binds.
This work, which was supported by the National Cancer Institute, is detailed in a paper titled, “Targeting bladder tumor cells in vivo and in the urine with a peptide identified by phage display.” An abstract of this paper is available through PubMed. View abstract.