Era of Hope 2011 Investigator Vignette

Title: Targeted Delivery of Gold Nanoparticles to Breast Tumors

Investigator: Oleg Andreev, PhD; University of Rhode Island

The main achievement during this study is development of peptides that target tumor acidity.

Most tumors, solid tumors and particular breast cancer tumors, they are acidic so they—they create an acidic environment because the cancer cells reach to the glycolytic pathway, and they create various acidic extracellular environment. This phenomenon is called the Warburg effect and Dr. Warburg got the Nobel Prize a long time ago for the discovery of this effect. But unfortunately the tumor acidity was not used as a target for—for treatment or diagnostic of tumors. And we—we worked in molecular biophysics field and mostly we are studying the folding of protein, membrane proteins, in particular, we’re studying membrane peptides insertion and folding. And we found one peptide which is soluble in water but in an acidic environment, it inserts in the membrane and forms alpha helix.

And this—then we know that the tumor is acidic and we ask it ourselves this peptide can be used for targeting of tumor acidic tissue. We call this peptide pHLIP, ph-low insertion peptide. And we labeled it with fluorescent dyes and just checked on the mice models and indeed these peptides can find tumors and they can accumulate in the tumor and we can see it using fluorescence imaging techniques.

And the next step was if we can deliver fluorescent dyes or imaging dyes or some drugs—what we’re doing, so maybe we can deliver nanoparticles as well to the tumor and use this opportunity to treat or improve diagnosis of cancer tumors using nanoparticles. The main results, which actually I’m presenting on this conference—that delivery of gold nanoparticles to the tumors.

Gold is attached to this peptide, and the peptide when it inserts, it forms helix. And in healthy tissue, it doesn’t insert it; it can bind weakly to the surface but then it detaches and in time it washed out. But this insertion, it makes very stable complex and this complex stays for several weeks actually.

And we can attach our peptide to these gold nanoparticles and then inject in the blood and see distribution in the tumors. So we found that indeed it reached the tumor and accumulate there and gold nanoparticles can be used for enhancement imaging for the diagnosis of tumors and also for enhancement radiation treatment because when you apply the radiation, gold can transfer this into Auger electrons it’s called and this Auger electrons, they can kill cancer cells.

So it increases efficiency of radiation therapy by itself and if you have much more gold accumulated in tumor tissue than in surrounding normal tissue, healthy tissue that means that you can decrease the radiation dose, and this would not affect much of the healthy tissue but would destroy the tumor tissue.

And also even some spot that you cannot identify, they will be marked the pHLIP nano-gold as well so total radiation beam you don’t need to focus exactly to the—to the tumor body but you can—you can apply it more—more widely to this area and kill any—any small tumors that are not even connected to the main tumor body.

And also the advantage that is—this gold is staying for a long time; you can—you can do this radiation therapy several times every day or maybe different frequency in time, and because this gold would stay here and you can use it many times. So if we deliver like I think 1,000 nano-gold particles, this would certainly maybe close to the 100% that these cancer cells will be destroyed by radiation. And we would not have these gold in the healthy cells so they would not damage much by this radiation. And we—also we can use less radiation than normally used right now in radiation oncology.

There is still a lot of work that needs to be done; particle size and particle shape is very important and it affects the efficiency of delivery. We’re working with some collaborators from Rhode Island Hospital and from Tufts University; they are medical doctors that are doing radiation therapy, and we hope that soon we will start experiments using nano-gold for radiation therapy.

This program, Breast Cancer Program, focused on the novelty of the approach. And I think supporting any novel—sometimes maybe crazy ideas—would lead to the breakthrough in breast cancer research in the future and right now.