The study, published in the journal Nucleic Acids Research, showed that when administered to the animal subjects, the particle, known as HPK, targeted tumor cells while leaving normal tissues untouched, according to Lali Medina-Kauwe, PhD, professor of Biomedical Sciences and corresponding author of the study.
Medina-Kauwe and her team focused on HER-3 type breast cancer cells that resist even the newest types of therapy designed to target the walls of cancer cells. Medina-Kauwe looked for a way to instead attack the insides of these cancer cells using a new tool, a type of genetic code called small interfering RNA or siRNA.
SiRNA interferes with a cell's functions by blocking protein production. It can disrupt or even kill targeted cells, according to Felix Alonso-Valenteen, PhD, postdoctoral fellow in the Medina-Kauwe lab and first author of the study.
So far, drugs that make use of siRNAs have been approved for only limited use in humans by the Food and Drug Administration, in part because getting siRNAs into tumor cells has proven difficult, Medina-Kauwe said. So she came up with an innovative idea to solve this problem: using the intrinsic ability of viruses to target and penetrate cancer cells.
By adapting protein capsules of adenoviruses, her lab created HPK—an engineered transport system that could deliver anti-cancer cargo and breach the cell walls of the tumors. Her team further manipulated HPK to make it automatically seek out tumor cells and to make the capsules appear tumor-friendly.
"We made use of the natural attraction and then utilized it—almost like biological judo—using the momentum of these naturally occurring molecules to accomplish what we wanted," Medina-Kauwe said. Analysis of in vitro results showed that HPK was able to get past tumor cell walls while leaving healthy cells intact.
Next, the team tested HPK in animals. Laboratory mice were implanted with cancer cells specially engineered to produce a light-emitting molecule. Then HPK, loaded with siRNA engineered to suppress production of that light-emitting molecule, was introduced into the mice. As the team had hoped, the siRNAs penetrated the tumor cell walls and switched off the light-emitting molecules.
The study demonstrated that HPK could deliver gene-silencing siRNAs inside tumor cells. "This adds a level of gene modulation that is not possible through conventional methods," Medina-Kauwe said.
While Medina-Kauwe's work is done at the molecular level, she keeps her eyes on the big picture. "The goal is to find critically needed treatments for patients who have difficult-to-treat cancers," she said. "Our study shows a possible way forward to improving patient outcomes, and we are committed to continuing our work on this front."
Funding: Research reported in this publication was supported by the National Cancer Institute and the National Center for Advancing Translational Sciences of the National Institutes of Health under award numbers R01 CA129822, R01 CA140995 and UL1TR000124; by the National Institutes of Health under award numbers T32 HL134637, CA129822, CA140995 and 8TL4GM118977-02; by the Department of Defense under award numbers W81XWH-06-1-0549 and W81XWH-15-1-0604; and by the Avon Foundation and California State University Northridge.
Conflict of interest statement: Medina-Kauwe and Cedars-Sinai hold significant financial interest in Eos Biosciences, Inc., of which Medina-Kauwe is co-founder and scientific advisor. A patent describing the HSi (HerSi) nanobiotherapeutic (US13/189,265) is pending.