Size Matters

(NHI Nanoblog) A new study tracking how inhaled nanoparticles move through the lungs and lymphatic system, then out of the body, offers more weight to the growing sense that even in a field defined by size, it matters how big something is.

Nanotechnology, of course, is all about size. Anything nano has to be super-small: the generally-accepted, if loose, definition covers particles under 100 nanometers. (One nanometer is a billionth of an meter.) At that size, particles take on super-properties that are now being used in new consumer and medical products.

When it comes to working with living organisms and nanoparticles, however, more and more scientists are finding that smaller is better if the material isn’t supposed to stick around in tissues or organs.

Now researchers at Beth Israel Deaconess Medical Center, part of Harvard Medical School, MIT and the Harvard School of Public Health are seeing the same thing, and finding that the surface chemistry of the particles also make a difference.

In a study published online this week in the journal Nature Biotechnology, researchers tracked how a variety of nanoparticles moved through rats after being inhaled. They used an assortment of different substances to get particles that were inorganic, organic, and of different kinds of surface charges, in addition to a variety of sizes.

What they found is that particles smaller than 34 nanometers moved easily into the rats’ lymph nodes. Particles smaller than six nanometers that were both positively and negatively charged (the scientific term is zwitterionic”) were able to move into the bloodstream, and then be cleared from the body through the urine.

Hak Soo Choi, a co-author of the paper and an instructor at Harvard Medical School, said in an e‑mail interview that the findings should help the development of drugs and medical therapies using nanoparticles — by helping researchers know what to use, and what to avoid, for particular conditions.

For example, Choi said, if getting medicine to the bloodstream is the goal, the very small particles would be useful. If a medical treatment needed to stay in the lung lymph nodes to be effective (for something like antibiotics for a lung infection) then the particles larger than 34 nanometers would be the choice.

However, he said, there are some safety issues raised in the study. Certain types of particles smaller than 34 nanometers, but larger than six nanometers, could be extremely dangerous since they wouldn’t leave the lymph nodes and then clear the body. If the even smaller materials have certain characteristics that wouldn’t caused them to leave the body, Choi said, they could simply keep circulating in the bloodstream, and can potentially reach every tissue and organ in the body.”

As medical researchers move forward with nano-based applications, Choi said, the fundamental question that one must answer before exploring any nanoparticle-based idea is whether the nano-scale’ is actually needed to solve the clinical problem at hand.

Given their relatively large size, high retention in the body, and potential toxicity, many classes of nanoparticles introduce more complexity than they may be worth.”

It’s already known that inhaling large quantities of carbon nanotubes—tiny cylinders that behave a lot like fibers — can cause mesothelioma, a disease associated with asbestos exposure. Researchers also have shown that other nanomaterials, such as nanosilver, can accumulate in water and other parts of the environment.

But as medical researchers enthusiastically embrace the promise of nano-based treatments, studies like this one offer a crucial perspective on what happens when these tiny materials interact with the organisms they’re supposed to treat, and what constitutes a safe treatment.

Along with Choi, the other authors of the paper are John V. Frangioni, Yoshitomo Ashitate, Jeong Heon Lee, Soon Hee Kim, Aya Matsui, Numpon Insin, Moungi G Bawendi, Manuela Semmler-Behnke, and Akira Tsuda.

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