Tratando o câncer como mecanismo

Infernal Mechanisms

At the nanoscale, the way that cancer spreads and kills can best be understood as mechanical processes. 

Nanotechnology and nanoscale mechanical engineering may soon lead to a revolution in oncology.

By Mauro Ferrari

The healing arts are often held up as a field in which the cold calculus of mechanical engineering has little purchase. Instead, we are told, medicine is a place where biology and chemistry hold the key insights. Sure, a bioengineer could fashion an artificial hip, but how could mechanical engineering hope to remedy the common cold, or cure cancer?

Anticancer therapy may soon be carried out using highly designed, 

multi-stage nanoscale particles. These particles would home in 

on tumors by seeking out cells that possess mechanical 

properties unique to cancers.

But in truth, engineering mechanics and mechanical engineering have long been present in oncology and cancer research. The last decade has provided ample illustrations of the diversity and depth of the mechanics-to-cancer connection.

For instance, Arun Majumdar in the Department of Mechanical Engineering at the University of California at Berkeley used micromachined cantilever beams to provide a means for the early and accurate diagnosis of cancer from biological fluid samples. With his team, Majumdar fabricated arrays of micro-beams using techniques employed in the field of microelectromechanical systems, then decorated their surfaces with antibody molecules that link specifically to conjugate molecules—so-called antigens. 

Certain proteins are markers of cancer because they are overexpressed in the blood and other fluids of cancer patients. Majumdar observed that the micro-beams deflect and change their resonant frequencies when antibodies bind to the antigen proteins. From such observations his team proved that it is possible to determine the quantity of several cancer markers in a blood sample, and thus produce a diagnosis with an accuracy and rapidity that is unmatched by conventional medical laboratory techniques. Thus, structural mechanics entered cancer diagnostics.

In a second example, Rakesh Jain and his team at Harvard University and Massachusetts General Hospital demonstrated that cancers and the surrounding tissues (what is known as the “cancer microenvironment”) generally develop internal hydrostatic pressure distributions that oppose the transport of therapeutic drugs from the blood stream into the cancer. This results in greatly diminished efficacy of treatment for cancer drugs, and calls for the development of new therapeutic approaches that can overcome the pressure gauntlets. Thus, solid and fluid mechanics entered cancer therapy.

Our own laboratories in Berkeley, Ohio State, and now in Houston have been active for many years in the field of mass transport inside nanopores and nanochannels, and have pioneered the field of nanofluidics. We developed novel methods for the fabrication of nanochannels in silicon membranes, with dimensional controls that are much better than those of the conventional photolithography used in MEMS. We employed sacrificial layer techniques to attain the goal of reproducibly fabricating channels with minimum dimensions of as few as five nanometers, and essentially with no upper dimensional limit. Over more than 10 years we established new predictive, mechanical laws that apply to these nano-environments, such as non-Fickian diffusion equations, and non-linear osmotic pressure relations.

Nanofluidics has a direct application to cancer therapy. For instance, we demonstrated that these nanochannel systems can be embedded into capsules implanted in the body to release anticancer drugs with the time control that is necessary to attain maximum efficacy with greatly reduced or eliminated adverse side effects. Controlled release with a constant rate can be attained with passive devices, just by exploiting the non-Fickian diffusion profiles. A time-variable rate of release can be obtained by applying a potential across the nanochannels, and employing the phenomenon of electro-osmosis, which becomes significant only in channels of nanometric dimensions. This affords the release of drugs in accordance with a preprogrammed profile, or by external activation, or ultimately, in a self-regulated manner that comprises on-board sensors, intelligence, and the release actuators. Such a device can be thought of as a biomimetic, mechanically engineered “nanogland.”

In addition to the increased efficacy and diminished adverse side effects that accompany the release of drugs only when needed, and at the small local concentration required at the site of the implant (rather than flooding the body), these personalized medicine nanoglands further afford the benefit of providing therapy away from the hospital setting. Such off-site treatment is particularly crucial for populations in remote and under-served geographical areas, or in such extreme settings as military combat zones, humanitarian relief missions, and space travel. Indeed, this potential has caught the interest of researchers in broad areas of medicine outside of oncology.
...

Read more here/Leia mais aqui: Mechanical Engineering Magazine