New Nanoparticle Cancer Therapy

quixote9 tips us to a BBC story on a promising new cancer therapy using targeted nanoparticles. From the article: "The researchers used the nanoparticles to zero in on the network of blood vessels that supply the tumors in mice with nutrients and oxygen... [They] developed a technique for amplifying [the nanoparticles'] homing ability by designing a multifunctional nanoparticle that binds to a protein structure found only in tumors and associated blood vessels... The tests showed that within hours of the injection, the artificial platelets began blocking the supply without harming normal tissues. The scientists believe the nanoparticles could also be used to carry drugs to the tumor."

Comments

When

[Swimport]

Every few months there is a cancer break through it seems. When are we finally going to see something in the hospitals? Is it the FDA and bureaucratic red tape, are these vapor cures? If its red tape, why not bring your drug down to Mexico, I'm sure plenty of cancer patients wont mind crossing the boarder for something that works. And if they every do cure cancer, invest all your money in Philip Morris.

Mathematical and Computational Modeling

[macklin01]

Some of my colleagues (e.g., Vittorio Cristini) have been modeling the potential benefits of nanoparticle drug delivery for a couple of years now. As has been known for some time (e.g., see papers from R.K. Jain), the blood vessels that grow to supply tumors with nutrients (the tumor-induced neo-vasculature) are different than regular, non-pathological vessels. They tend to be more tortuous and leaky, with larger holes than regular vessels.

This is where the nanoparticles come in: one can design nanoparticles that encapsulate cancer drugs in particles that are too large to exit normal blood vessels but can pass through the leakier, tumor-induced blood vessels. This naturally targets cancerous tissues.

However, there are other issues to consider. Due to the high pressure inside tumors (due to the rapid proliferation of cells within a confined area, among other factors), along with the leaky vessels, blood flow can be very poor inside a tumor, and so while the drug may be targeted toward and delivered to the tumor, it may not actually penetrate very far into the tumor. Some great work has been done by Steven McDougall, Sandy Anderson, and Mark Chaplain in this area. In particular, look at their DATIA (dynamic adaptive tumour-induced angiogenesis) papers.

One way around this (suggested by R.K. Jain and Vittorio Cristini, among others) is to use targeted anti-angiogenic therapy to prune out the worse blood vessels and improve flow within the tumors, thereby also improving drug delivery and penetration.

Lastly, on the therapeutic aspect of blocking up tumor blood vessels with the nanoparticles, the work we've done (see this paper, which will appear in the Journal of Theoretical Biology soon), indiscriminately cutting off the nutrient supply to a tumor can increase tumor invasiveness by increasing morphological (shape) instability. (See some of the animations here.) So ironically, while more tumor cells may be killed, those that remain may spread farther and initiate new tumors. Given that hypoxic tumor cells are more likely to be resilient to further treatment (e.g., hypoxic breast cancer cells), this is a problem worth keeping in mind when planning anti-angiogenic therapy.

If you're interested in these topics, please do check out the paper above. (You can also download it at my website without any special memberships.) Even if you don't like it, we have a lot of references you may find handy. -- Paul