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Wednesday, October 04, 2006

Cell-Like Nano Particles for Attacking Disease

Researchers are developing smart "nanocarriers" for drug delivery and diagnostics.

By Kevin Bullis

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In this idealized image, engineered nanocarriers find and attack specific diseased cells. The stick-like objects allow the nanocarriers to bind to particular cells. (Courtesy of Patrick Hunziker, University of Basel, Switzerland)

Using parts of living cells in a smart nanotechnology-based system, researchers in Switzerland have demonstrated a "nanocarrier" that can target specific types of cells and light up in response to conditions in their immediate environment.

The work is part of a growing effort by scientists worldwide to develop nano devices that can circulate in the bloodstream, slip stealthily past the body's immune system, attach to cancer or inflammatory cells (an important ability in diseases such as atherosclerosis and arthritis), and deliver a deadly drug payload--destroying some of the toughest diseases without the often debilitating side effects that can accompany chemotherapy (see "Nanomedicine").

Already, early versions of such nano-based treatments have been approved for breast cancer. But Patrick Hunziker, a physician at University Hospital Basel, and Wolfgang Meier, professor of chemistry at the University of Basel, are attempting to trigger the release of the drugs at more precise locations and at release rates adjusted to have the most effect on a particular disease.

One promising approach to achieving this goal is to develop nanocarriers that can respond to cues in their immediate environment, similar to how living cells can open and shut membrane pores. Hunziker and Meier have just reported in the journal Nano Letters on a system that incorporates bacterial proteins that form such pores.

The researchers first developed a type of polymer that self-assembles to form hollow spheres about 200 nanometers across. During the assembly process, they introduce the pore proteins, which form channels in the polymer spheres. As in bacteria, where the pores can close to protect cells from acidic environments, these channels also open and close in response to changes in pH.

The researchers then demonstrated that the resulting nanocarrier could control the location and duration of a fluorescent signal--an ability that could be useful in lab diagnostics. To do this, they added another biological molecule to the mix, encapsulating within the spheres an enzyme that breaks down certain compounds, causing them to glow. They then added the nanocarriers to a solution containing these compounds.

In experiments in which the researchers add the enzymes directly to the solution, without using the nanocarriers, the compounds glow diffusely and for only a few minutes. When using nanocarriers, though, the light is concentrated within the spheres, where the enzymes are sequestered, and the signal lasts many times longer--about three hours. Combined with the ability (demonstrated in an earlier paper) to make the nanocarriers latch onto specific cells, the system could be used to highlight the location of these cells in lab tests.

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Comments

  • Further Engineering
    smooresdel on 10/06/2006 at 9:35 AM
    Posts:
    1
    I wonder whether it would be possible to further engineer the carrier to release a chemical signal that would enhance attraction to the attached site by other nanocarriers similar to the way that foraging ants signal to other foraging ants, "I am a nanocarrier who has found a target" and so on? The nextreceiving nano carrier would also release to chemical signal, "I am a nonocarrier who has found a nanocarrier who has found a target."
    Rate this comment: 12345
    • Re: Further Engineering
      Kevin Bullis2 on 10/06/2006 at 10:11 AM
      Posts:
      3
      Interesting idea.  I'll ask that question in my next interview on this subject.
      Rate this comment: 12345
      • Re: Further Engineering
        fabiofais on 02/25/2007 at 10:38 AM
        Posts:
        1
        Hello, thank you for the article and the interesting thread. I would like to contribute telling you that there is actually a system similar developed by S. Bahtia at MIT (ref: Harris, T., Maltzahn G.V., Derfus A., Ruoslahti E., and Bhatia S. Proteolytic Actuation of Nanoparticle Self-Assembly. Angewandte Chemie 45:3161-3165, 2006)that implements that idea. These particles do not exactly release attractant signals, but they do expose it under the influence of specific proteases, allowing enrichment in a desired site where a first set of particles are localized (refer to the following link: http://www.burnham.org/images/Ruoslahit%20Cancer%20Cell%202002.JPG figure published in Cancer Cell, 2002 Aug;2(2):97-8).
        I have the pleasure to work in this amazing field of drug delivery, and the former is one of the papers I trust as a milestone in developing pharmaceutical preparations for drug delivery.

        Fabio Fais
        Rate this comment: 12345
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