Nanotech Trojan Horse That Kills Cancer

An anonymous reader writes "University of Michigan scientists have created the nanotechnology equivalent of a Trojan horse to smuggle a powerful chemotherapeutic drug inside tumor cells - increasing the drug's cancer-killing activity and reducing its toxic side effects." From the article: "The drug delivery vehicle used by U-M scientists is a manmade polymer molecule called a dendrimer. Less than five nanometers in diameter, these dendrimers are small enough to slip through tiny openings in cell membranes. One nanometer equals one-billionth of a meter, which means it would take 100,000 nanometers lined up side-by-side to equal the diameter of a human hair."

Comments

Nanoparticles?

[Raindance]

The real news here, if I can interpret the press release correctly, is not that the nanoparticle is the trojan horse, but that its small size *allowed* the researchers to construct the trojan horse.

The article summary is a bit brief- basically, cancer needs a lot of folate. Moreso than normal cells. These folks attached both an anti-cancer drug and a bunch of folate to a nanoparticle, which, due to both its small size and tasty-looking folate, is able to enter cells and deliver the anti-cancer payload rather than slowly diffuse it through the cell wall.

This is still a bit of a shotgun approach, as normal cells still get targetted to some extent, but *much* less so than previous methods.

Re:Nanoparticles?

[TGK]

A little more background....

Cancer cells divide more rapidly than normal cells (that's part of what makes them cancer). To divide they need to synthesize DNA and to do that they need that tasty looking folate you talked about.

Thus, cancer cells absorb more folate than normal cells.

Traditional chemotherapy drugs attack dividing cells, exploiting the conditions present in a dividing cell to kill it. Because cancer cells are dividing more often than normal cells, they are disproportionately targeted. Poof -- chemo works.

This new technology incorporates the same kinds of drugs, but makes cancer cells more likely to absorb the drug, making it even more biased towards killing off cancer cells. Normal cells will absorb at a slower rate and will still be largely unaffected unless they are dividing. Cancer cells will absorb more, and be hit harder by the drug.

It basicly allows us to focus the drugs more. That's a good thing. More focus == less side affects. That means less weight loss, less hair loss, less vomiting, etc.

All those things mean increased dosages are possible - which means we can kill the cancer faster and more effectively.

Re:How do they determine cancer/non cancer cells?

[TripMaster Monkey]

From TFA:

Dendrimers have a tree-like structure with many branches where scientists can attach a variety of molecules, including drugs. In experiments reported in Cancer Research, U-M scientists attached methotrexate, a powerful anticancer drug, to branches of the dendrimer. On other branches, they attached fluorescent imaging agents and their secret ingredient - a vitamin called folic acid.

Folic acid, or folate, is an important vitamin required for the healthy functioning of all cells. But cancer cells, in particular, seem to need more than average amounts. To soak up as much folate as possible, some cancer cells display more docking sites called folate receptors on their cell membranes. By taking advantage of a cancer cell's appetite for folate, U-M scientists are able to prevent the cells from developing resistance to chemotherapeutic drugs.

Wow, really wow.

[borkus]

Most folks know someone either in their family or circle of friends who's had chemotherapy. Depending on the level of treatment, it can be grueling. The impressive quote from the story is this -

the nanoparticle-based therapy using folic acid and methotrexate was 10 times more effective at delaying tumor growth than the drug given alone. Nanoparticle treatment also proved to be far less toxic to mice in the study than the anticancer drug alone

Less toxic and 10 times more effective (possibly requiring fewer treatments). I wonder if that could make it a viable treatment alternative for inoperably cancers.

Lastly, some folks asked about what happens to all those dendrimers when they've done their job.

The results showed that the kidneys quickly filtered free nanoparticles from blood and eliminated them in urine. The researchers found no evidence that nanoparticles were able to leave the bloodstream and enter the brain.

for HIV

[Anonymous Coward]

I read today morning that they are using dendrimers for preventing HIV from infecting T-cells.

HIV cells have certain receptors on the surface. those receptors are used to open a doorway into T-cells (our soldiers). Some molecules that target HIV receptors are attached to the dendrimer and then the dendrimer is released into the body. when the dendrimer gets to the HIV cell, the molecues bind to receptors and block their action of infecting healthy cells.

Re:How it works

[TripMaster Monkey]

They put the poison in the folate.

Actually, strictly speaking, they put the poison next to the folate. That's what the nanotech dendrimers are for...to provide a means to mount two substances next to each other that wouldn't naturally combine.

Re:How do they determine cancer/non cancer cells?

[harryk]

Unfortunately the article explains quite clearly that ALL cells require folate (folic acid), however cancer cells will eat it up like its going out of style. While some good cells will still absorb/receive the poisoned payload of the dendrimer, the cancerous cells will want to eat the absorb them first. Once the dendrimer (the nanotech peice of the whole article) is absorbed, the folate is absorbed by the cancer cell, and then (not necessarily in this order) the methotrexate is absorbed, which is the cancer fighting drug. The idea is that the focused (not completely, but moreso) attack on the cancer cell will reduce the side effect of the methotrexate. The problem with today's delivery method is that all cells (good and bad) are evenly targeted with methotrexate. This is great use of an updated delivery method, but the cancer killing drug is something that has been around awhile. Great article! harryk

Re:How it works

[dannyitc]

Folate is a molecule needed for DNA synthesis. Cancer cells need more of it because they are multiplying uncontrolled and therefore are synthesizing much more DNA than regular cells. Folate in itself, however, is not a mutagen, which is required to disrupt the DNA in a healthy cell to make it become cancerous. Actually, increased folate intake has shown to decrease instances of many types of cancer because folate deficiency is a main cause of error in DNA synthesis.

Re:Okay, but where's the grey goo?

[dfn5]

Okay, but where's the grey goo?

Wrong kind of nanotech. If you read the article you would've seen that all they have developed is a polymer molecule. The "grey goo" would come from nano machines that self replicate. That has nothing to do with this.

Re:Medical nanotech

[maggard]

Based on what I understand of nano-tech and the human body, I think we're going to see a lot more of this, and this will be the first medical nanotech revolution: Creating drugs that are targetted only at the things they are supposed to affect.

Except it's not.

These nano-particles with Folic Acid go into cells all over the body along (though apparently don't cross the blood/brain barrier). It's just that cancer cells pull in more FA, thus more nano-particles, thus more nanoparticle chemotherapy payload. However every cell that uses FA is getting some slight dose, proportionial to their FA usage.

So, contrary to your hopes, it is:

... flooding the entire body with something to affect .1% of it ...

But thanks for posting, and the rest of your ideas are right on, if only you weren't 180 degrees wrong about the article.

Re:OLD NEWS..

[Anonymous Coward]

"In a related trail, (refer: http://www.pedsdoc.com/index.php?name=News&file=ar ticle&sid=12 [pedsdoc.com]) in 1999, 18-year-old Jesse Gelsinger died during a gene therapy clinical trial at the University of Pennsylvania...."

Related how? The study from TFA is a directed drug delivery study using as a carrier a non-immunogenic (in mice, anyway) man-made dendromer. The Gelsinger trial was a gene therapy trial using adenovirus (a common cold virus) as a vector to carry corrective DNA to cells. IIRC, Gelsinger had an extreme immune reaction to the vector, a fairly common occurance when using as a vector a virus that the immune system has almost certainly seen previously and been primed to combat. These studies are quite different from a physiological/immunological standpoint.

Other Nano-enabled Drugs Already Available

[Alan Livingston]

I sent the link to my wife, an Oncology Nurse Practitioner. She said that this type of transport mechanism isn't all that new.

She went on to say that they've already packaged Taxol (a breast CA chemo) in a similar way and supplied this link for more info. It's called Abraxane.

Re:Other Nano-enabled Drugs Already Available

[4nd3r5]

nurse smurse...

Abraxane is a fancy new package for a well known drug (taxol) it has nothing to do with the treatment in the article. What it does is reduce the complications with taxol treament, but not the efficiency. It allows for the dose to be increased, and thereby is more efficient

The treatment in the article is something quite difrent, it increases the concentration in the target/cancer cells. This reduces the side effects of the treatment. Its new and it is brilliant.

Yes my spelling sucks... but i have a dictaphone..

Re:yuck...

[iamlucky13]

"It's like a Trojan horse," Baker explains. "Folate molecules on the nanoparticle bind to receptors on tumor cell membranes and the cell immediately internalizes it

According to that passage, it's not quite as simple as slipping through the cell membrane, like osmosis of water. It sounds like they're taking advantage of facilitated transport. Your cells need some molecules that are too large to fit through your cell membrane, so instead there are "gates" for them to pass through that are essentially proteins embedded in the membrane. Each gate can bond to a particular molecule, so you theoretically don't have stuff getting through that shouldn't. When the molecule bonds to the protein, it changes shape, taking the molecule in, typically without the expenditure of ATP (cell energy).

I'm curious, what exactly about this makes you feel uncomfortable?