Harnessing Nanoparticles For Targeted Cancer Treatment A new approach to cancer therapy uses nanoparticles of fat to deliver a working copy of a tumor suppressor gene to tumor cells, making the tumors more vulnerable to conventional cancer treatments. Esther Chang of Georgetown University Medical Center describes the research, which is now undergoing safety trials.

Harnessing Nanoparticles For Targeted Cancer Treatment

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IRA FLATOW, host:

This is SCIENCE FRIDAY from NPR News. I'm Ira Flatow. A bit later in the hour, we'll talk about some synthetic biology news and some green do-it-yourself projects. You'll want to be around for those.

But first, some cancers respond well to treatment. Others, though, are more stubborn, with tumors that spread or regrow. Well, this week, speaking at the Experimental Biology 2009 meeting in New Orleans, researchers presented one interesting approach that might help target those resistant tumors, delivering gene therapy straight into the tumor cells by using nanotechnology. Joining me now to talk about it is Esther Chang. She's a professor of Oncology and Otolaryngology at the Lombardi Comprehensive Cancer Center. That's at Georgetown University Med Center in Washington. She joins us by phone from her office there.

Welcome to SCIENCE FRIDAY. Dr. Chang, are you there?

Dr. ESTHER CHANG (Professor, Oncology and Otolaryngology, Georgetown University Medical Center): Oh, hi, Ira.

FLATOW: Hi, there.

Dr. CHANG: Thank you so much for having me.

FLATOW: You're welcome. Let's talk about your basic delivery system. Is this really just a delivery system to get genes using tiny nano - to deliver genes getting - using tiny nanoparticles of fat?

Dr. CHANG: Yes. Actually, you know, you could consider them as tiny nano - little FedEx trucks.

(Soundbite of laughter)

FLATOW: I could see the commercial now.

Dr. CHANG: Right.

(Soundbite of laughter)

Dr. CHANG: For a number of years that my lab has been involved in the study of genetic factors in cancers, resistance to radiation therapy or chemotherapy, and then a very strong correlation has been shown by many teams of investigators between the etnomology, the malfunctioning of certain genes and tumors, resistance to these conventions against therapy - so more recent years that we have been exploring different methods to target these malfunctioning genes.

FLATOW: Is there one gene in particular we think of more than the others?

Dr. CHANG: Actually, I'm sort of partial…

(Soundbite of laughter)

FLATOW: Yeah.

Dr. CHANG: …towards a tumor-suppressor gene, PCp3.

FLATOW: Oh, we've heard about that one.

Dr. CHANG: Yes, great.

(Soundbite of laughter)

FLATOW: P53, if it's not working right, it doesn't suppress the growth of tumors.

Dr. CHANG: That's exactly right. And it has such a pivotal function in controlling cell growth and actually repairing damages to the cells. When it's not functioning - and it just cannot protect the normal cells from turning into a cancer cell.

FLATOW: So your technique, then, using this FedEx nanoparticle technique, is to deliver the healthy, so to speak, gene into the cell.

Dr. CHANG: Exactly. Well, the reason you might want to ask me is why FedEx truck?

FLATOW: Okay. Why not UPS, you know?

(Soundbite of laughter)

Dr. CHANG: That's right. UPS could do it, too. Both of them, actually has a commonality. That is, they have a specific address. So they know which household they're going to deliver their goods to, letter or other items. The conventional cancer therapy is if you will call it like a crop duster, if you want to have a message sent to a specific area, well, one of the ways, which now there's - I don't think we do it that way - is print out the messages in small slips of papers. And you use a crop duster to send a message out.

FLATOW: Right.

Dr. CHANG: Well, the intended family may get it, but you also send it out to a lot of families that don't really - are intended to get the message. So those families, we call them normal tissues, normal cells. So this is the very, very critical reason that we need to target the therapeutics to the tumor cells specifically - not only to the primary tumors, but also to the distant metastasized tumor, no matter where they are.

FLATOW: Yeah.

Dr. CHANG: And it has to - the therapy, to be effective, has to be able to be delivered to these spread metastatic cells.

FLATOW: So you have to put it into the blood stream, then…

Dr. CHANG: Exact…

FLATOW: …to get them everywhere in the body where these bad tumor cells might be.

Dr. CHANG: We don't know where they are, so it has to go through the bloodstream. So it has to travel through the bloodstream. Well, it has to have a capability to recognize which is the target cells, which is the tumor cells. Whenever they see their target cell, they enter and they deliver the payload. So we have been engineering these targeted nanoparticles for the last 10 years or so. The component of these nanoparticle is quite simple. Like you said, these are fat droplets. These are synthetic material easily self-assembled, easily degradable, and using that as a little container, little vehicle. And we decorate it, this little fat droplets, with the - with a targeting (unintelligible), if you will, on the surface.

So give them the capability of home to the tumor cells whenever they see - essentially, when they're traveling. They see one, they home into it, they deliver.

FLATOW: They go right through the cell?

Dr. CHANG: Actually, they start engage on the cell's surface, and we go through a mechanism we call the receptor-mediated endocytosis to get the payload and get the drug or the genes or the small molecules into the tumor cells.

FLATOW: And have you actually tested this out yet in people?

Dr. CHANG: Yes. We just started, I should say that we started about a year ago, our phase one trial in patients with advanced solid tumors - all kinds of solid tumors. And this is being done by my collaborator, Dr. John Nemunaitis at Mary Crowley Medical Research Center at Dallas, Texas.

FLATOW: Mm-hmm. So this could be useful for all kinds of solid tumors.

Dr. CHANG: We have tried in our laboratory in experimental animals models, we have tried 15, 16 different kinds of solid tumors - breast, prostate, bladder, lung, colon, melanoma, cervical cancer. So 15, 16 different kind of tumor model we tried. And we also have approved - we actually tested in six patients already. As you know, a phase one trial, clinical trial, is for safety's sake.

FLATOW: Right, right.

Dr. CHANG: And so we escalate the doses. And so we start with a very low dose. And now we're able to actually get up to six times of our initial dose. And the safety profile has been looking quite good.

FLATOW: Do you have any preliminary studies from them that say, hey, even with the phase one they got a little better?

Dr. CHANG: Yes. We're very optimistic to this potential of this trial. As you know, this is the very, very early stages, and we really, you know, cannot make any conclusion or suggestion at all.

FLATOW: Right.

Dr. CHANG: But so far, we are happy.

(Soundbite of laughter)

FLATOW: Wow. We don't want to get people's hopes up too much, because so many people are listening.

Dr. CHANG: No, we cannot. This is very early stages in our investigation.

FLATOW: But you will be dosing it up a little higher.

Dr. CHANG: We have been. Actually, we will be able to get into the patients with six times higher doses than our initial dose.

FLATOW: And when do you move to phase two, then?

Dr. CHANG: I'm hoping within a year.

FLATOW: Wow. Wow.

Dr. CHANG: You know, hoping.

(Soundbite of laughter)

FLATOW: Hoping.

Dr. CHANG: Right.

FLATOW: But in the lab animals, you've had good results.

Dr. CHANG: We have very, very good results. Actually, our end point is not to see whether our treatment is going to slow down the tumor growth in these animals. Our end point is elimination, because if you can only slow down the tumor growth, then the treatment, eventually you have to - we still have to deal with the slow-growing tumors.

FLATOW: Sure.

Dr. CHANG: So we need to eliminate a tumor. That's our end point.

FLATOW: Have you had that in animals?

Dr. CHANG: Yes. Many, many, many times.

FLATOW: Wow. I'm speechless. It's not often.

(Soundbite of laughter)

FLATOW: And I don't want to get anybody's false hopes up on this.

Dr. CHANG: No, these are animal models, as you know. That's why we need to do these clinical trials in patients.

FLATOW: And one of the keys here is nanotechnology.

Dr. CHANG: Actually, this is truly nanotechnology enabling, and also the key of targeting - because as we just talked about without targeting, really you're wasting not only a lot of material, it goes to places that you don't want it to go. And also, you also induce so much of the side effect that we often see in patients, so targeting - target it to the tumor cells specifically is our strategy.

FLATOW: You know, I've been covering medical stories for almost 40 years, and I keep hearing about the quote-unquote "magic bullet." You've heard it, too, I'm sure.

Dr. CHANG: Yes. I don't think this is the magic bullet.

FLATOW: This is not it.

Dr. CHANG: I think that the design of this specific nanomedicine is to augment the conventional cancer therapy, either radiation therapy or chemotherapy.

So we would like to deliver specifically tumor-targeted, a molecular therapy, which will render these tumor cells more sensitive to radiation treatment or chemo treatments. So we believe that this specific nanomedicine should be in combination with one of the conventional cancer therapy.

FLATOW: Why could you not deliver a drug that kills the tumor totally without the need for that?

Dr. CHANG: You're saying why couldn't we actually deliver also a chemotherapeutic agent?

FLATOW: Yeah.

Dr. CHANG: Yes. We are doing it exactly, and we're seeing very good results in animal models.

FLATOW: Ah, we haven't gotten to that point in humans yet.

Dr. CHANG: No, not in humans yet.

FLATOW: Not in humans yet, but that's what you meant by the good success in animals.

Dr. CHANG: Right.

FLATOW: Ah. So we're still doing the helper one and phase one, and we're waiting for phase one for the animal sort of models.

Dr. CHANG: Exactly.

FLATOW: Wow.

Dr. CHANG: No, no. We - this - our prototype, if you will, delivering the PCp3 is already in phase one.

FLATOW: Wow.

Dr. CHANG: And this - actually, technology turned out to be a platform technology.

FLATOW: That's great.

Dr. CHANG: When we switch the…

FLATOW: Dr. Chang, I've run out of time.

Dr. CHANG: Okay.

FLATOW: But we will get back - we will follow this, okay?

Dr. CHANG: Okay.

FLATOW: Do you promise to come back and keep us informed of how this is working out?

Dr. CHANG: Love to talk to you again, Ira. Thank you.

FLATOW: Thank you. Dr. Esther Chang of Georgetown University Medical Center in Washington. We're going to take a short break. We'll be right back after this. Stay with us. Don't go away.

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