Materials Science Versus Oxidative Stress

A little while back, I took a look at using the big stick of materials science to manipulate biochemical states in the body - starting with efforts to build a better antioxidant:

Oxidative stress is believed to play a role in neurodegenerative diseases such as Alzheimer's and Parkinson's. Some of the symptoms of aging such as arteriosclerosis are also attributed to free-radical induced oxidation of many of the chemicals making up the body. Despite the broad role that oxidative stress plays in human disease, medicine has been limited in its development of treatments that counteract free radical damage and the ensuing burden of oxidative stress. In contrast, in the field of engineering, considerable effort has been developed to counter the effects of oxidative stress at the materials science level. ... Our initial results suggest that cerium oxide nanoparticles extend cell and organism longevity through their actions as regenerative free radical scavengers. Additional studies suggest that these nanoparticles are also potent anti-inflammatory agents. Although much work remains to be done in this realm, ceria nanoparticles hold high promise for future development of nanopharmacological agents to treat age related neurodegenerative disorders and inflammatory disorders.

This sort of initiative is but a tiny step on a very long path that leads to nanomedical robotics, artificial blood cells a thousand times better than the real thing, and even more impressive feats of engineering. But you have to start with what is presently possible. Some more on cerium oxide in this paper:

Treatment of Neurodegenerative Disorders with Radical Nanomedicine:

Here, we summarize the work on the biological antioxidant actions of cerium oxide nanoparticles in extension of cell and organism longevity, protection against free radical insult, and protection against trauma-induced neuronal damage. We discuss establishment of effective dosing parameters, along with the physicochemical properties that regulate the pharmacological action of these new nanomaterials. Taken together, these studies suggest that nanotechnology can take pharmacological treatment to a new level, with a novel generation of nanopharmaceuticals.

"Radical nanomedicine" means different things to different folk of course - anything from the mass-produced artificial blood cell nanomachines of the 2030s to next year's application of somewhat better and more useful nanoparticles. But the trend towards engineering your way out of unwanted biological conditions at the scale of molecules and cells is very welcome and to be encouraged. Engineers put the pieces together and get the job done - don't underestimate the power of that approach to problems.

One caveat on any work involving antioxidants is the evidence produced to date indicating that it matters greatly where your antioxidants do their work. Are they meandering around uselessly, far from the points at which oxidative stress is generated or causing damage? Are they interfering in the signaling mechanisms that actually use oxidizing molecules?

Rabinovitch's group genetically engineered mice to produce a natural antioxidant enzyme called catalase. The mice lived 20 percent longer than normal mice - on average they lived five and a half months longer than the control animals, whose average life span was about two years ...

We had differing hypotheses about where putting catalase might do the best in terms of the advantage to life and health of the mice," Rabinovitch explains. So they targeted the gene in three different places in the mouse cells - the cytoplasm, the nucleus - where they thought it might protect the all-important DNA of the cell - and the powerhouses of the cells, the mitochondria - where cells "burn" glucose for energy and churn out high levels of these oxidizing free-radicals. The mice that lived longest had the gene in their mitochondria.

Here's another approach indicating that it matters where you put your antioxidants:

Instead of gene therapy, Skulachev's group has found a viable biochemical strategy for effectively localizing ingested antioxidants in the mitochondria; clever.

But if you're a clever engineer, this is all just another challenge to build around.

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