New Nanoparticle Could Provide Simple Early Diagnosis Of Many Diseases

Researchers have created a new nanoparticle that could someday act as a virtually all-purpose diagnostic tool to detect many inflammatory diseases in their earliest stages, including heart disease, Alzheimer's, and arthritis. The specially-designed nanoparticles seek out hydrogen peroxide (thought to be overproduced in trace amounts in the early stages of most diseases that involve some sort of chronic inflammation in the body), and emit light when they encounter it.

The actual reference...

[kebes]

The press release [gatech.edu] from Georgia Tech has a bit more information. The paper of this work will appear in the October issue of Nature Materials, but is already available online (for subscribers only, unfortunately):
In vivo imaging of hydrogen peroxide with chemiluminescent nanoparticles [nature.com] Dongwon Lee, Sirajud Khaja, Juan C. Velasquez-Castano, Madhuri Dasari, Carrie Sun, John Petros, W. Robert Taylor & Niren Murthy. Published online: 19 August 2007; doi:10.1038/nmat1983 [doi.org]

The paper describes the advantages of their nanoparticles:

The peroxalate nanoparticles have several attractive properties for in vivo imaging, such as tunable wavelength emission (460-630 nm), nanomolar sensitivity for hydrogen peroxide and excellent specificity for hydrogen peroxide over other reactive oxygen species.

In the paper, they demonstrate the use of this photo-marker in live mice, and are able to image the location of hydrogen peroxide anywhere in the mouse body. An obvious question regarding the technique is the toxicity of the nanoparticles. They do not discuss this in the paper (it will probably be the subject of an upcoming study), but the particles are ester polymers, with embedded dye (a pentacene derivative). So they are not using heavy-metal nanoparticles: these are peroxalate polymers. I'm not an expert in biocompatibility, but from the chemical structure, I wouldn't expect it to be highly toxic (it probably even degrades in the body).

Obviously a detailed toxicity study would be required before use in humans. However it's possible that it could be rapidly adapted to ex-situ diagnostics (e.g. on tissue explants) and then be adapted to live in-situ imaging if/when it is determined to be safe.

Re:Sounds like nonsense

[Anonymous Coward]

Heart disease and heart attacks certainly DO have a lot to do with inflammation. see the anti-inflammatory properties of lipitor, and see also the use of high-dose statins in the setting of acute MI. also, educate yourself on the pathophysiology of atherosclerosis and the role of macrophages.

Re:Sounds like nonsense

[kebes]

In the actual paper [nature.com], they mention:

The overproduction of hydrogen peroxide is implicated in the development of numerous diseases 1-4 and there is currently great interest in developing contrast agents that can image hydrogen peroxide in vivo.

and:

The overproduction of hydrogen peroxide is implicated in the development of numerous inflammatory diseases, such as atherosclerosis, chronic obstructive pulmonary disease and liver hepatitis 23-27.

The implicated references, if you care, are:

1. Lim, S. D. et al. Increased Nox1 and hydrogen peroxide in prostate cancer. Prostate 62, 200-207 (2005).
2. Chang, M. C. Y., Pralle, A., Isacoff, E. Y. & Chang, C. J. A selective, cell-permeable optical probe for hydrogen peroxide in living cells. J. Am. Chem. Soc. 126, 15392-15393 (2004).
3. Miller, E.W., Albers, A. E., Pralle, A., Isacoff, E. Y. & Chang, C. J. Boronate-based fluorescent probes for imaging cellular hydrogen peroxide. J. Am. Chem. Soc. 127, 16652-16659 (2005).
4. Albers, A. E., Okreglak, V. S. & Chang, C. J. A FRET-based approach to ratiometric fluorescence detection of hydrogen peroxide. J. Am. Chem. Soc. 128, 9640-9641 (2006).
23. Polytarchou, C., Hatziapostolou, M. & Papadimitriou, E. Hydrogen peroxide stimulates proliferation and migration of human prostate cancer cells through activation of activator protein-1 and up-regulation of the heparin affin regulatory peptide gene. J. Biol. Chem. 280, 40428-40435 (2005).
24. Laurent, A. et al. Controlling tumor growth by modulating endogenous production of reactive oxygen species. Cancer Res. 65, 948-956 (2005).
25. Stone, J. R. & Collins, T. The role of hydrogen peroxide in endothelial proliferative responses. Endothelium-New York 9, 231-238 (2002).
26. Mohler, D. L. & Shell, T. A. The hydrogen peroxide induced enhancement of DNA cleavage in the ambient light photolysis of CpFe(CO)(2)Ph: A potential strategy for targeting cancer cells. Bioorg. Med. Chem. Lett. 15, 4585-4588 (2005).
27. Hirpara, J. L., Clement, M. V. & Pervaiz, S. Intracellular acidification triggered by mitochondrial-derived hydrogen peroxide is an effector mechanism for drug-induced apoptosis in tumor cells. J. Biol. Chem. 276, 514-521 (2001).

I'm not an expert in these matters, but looking over the paper, it seems that there is considerable interest in this diagnostic technique for a variety of conditions. (The fact that it was published in a high-profile journal like Nature Materials is already a good indication.)

Re:New Light Source

[kebes]

The short answer is: no.

The paper uses well-established chemistry to generate light-emission. They basically have an ester (peroxalate) polymer with a fluorescent dye (a pentacene derivative). A chemical reaction with hydrogen peroxide (H2O2) changes the peroxalate groups into dioxetanedione groups. This irreversible chemical reaction leads to excitation of the fluorescent dye, and hence light emission.

The hydrogen peroxide is not really the energy source for the luminescence: it is more like a catalyst that enables the peroxalate groups to convert and thereby generate light. For use in a light-emitting device, you would need a large amount of peroxalate in addition to the hydrogen peroxide. Since the peroxalate is used up, you'd have to keep replenishing it.

Basically, there are easier (cheaper) ways to generate light!

However as a diagnostic tool this is great. The paper describes the use for medical imaging, but I see no reason why this couldn't be used for detecting peroxide in other situations, such as for forensics or detecting industrial leaks or contamination. (Then again, in non-medical contexts there are probably existing detection techniques that I'm not aware of.)

Re:Sounds like nonsense

[philip_bailey]

Most cancers, Alzheimer's and heart disease have nothing to do with inflammation, chronic or otherwise.

Actually, atheroma [wikipedia.org], the cause (in nearly all cases) of coronary artery disease, and the single commonest cause of death in the Western world, is well established to be an inflammatory process. The process of developing atheroma is influenced by a number of risk factors (e.g. diabetes, hypertension, hyperlipidaemia, smoking, obesity, family history); interestingly, rheumatoid arthritis is also a significant risk factor. It has even been hypothesised that various bacterial infections (which cause inflammation) may be a cause or risk factor for atherosclerosis, though studies looking at antibiotic treatment of these purported infections have not borne this out so far.

Re:Ever seen a girl with a real post-orgasmic glow

[fractoid]

I do not think it means what you think it means. [wikipedia.org]