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Engineered Molecules for Smarter Medicines

Specially designed polymers can dodge the body’s immune defenses to deliver vital medicine where it is needed most.

Darlene K. Taylor, Uddhav Balami

Although we rarely think about it as we fill a prescription at the drugstore or refill an order through an online service, delivering medicine to its intended site inside the human body is an elaborate problem in materials science.

The challenge begins the moment a drug enters the digestive tract or the bloodstream. The body naturally strives to defend itself against foreign invasion, even if the invasive substance is a lifesaving medicine. Some of our inner defenses work strategically to destroy invading agents at the molecular level, such as the antibodies launched by the immune system that attack unfamiliar entities in the bloodstream. Others act more like physical walls to tightly regulate intruding agents, such as the blood-brain barrier, a dense network of capillaries that separate the brain from circulating blood.

2014-03TaylorF1p111.jpgClick to Enlarge ImageEven if a therapeutic compound clears these hurdles, it may still fail in its mission if it is prevented from dissolving properly, or even if it dissolves too quickly and is cleared from the body before it can act. When an effective drug reaches the correct location in the body, at the right concentrations, and continues to work for the optimal amount of time, this represents the finish line of a very long obstacle course.

Some drugs manage to travel smoothly to their target site, whereas others are beset with challenges all the way. Unfortunately, this second category includes drugs that are vital to preventive care for some of the most lethal diseases, such as cancer. To develop more effective therapeutic agents, researchers need to come up with not only viable drug candidates but also adaptive materials for drug delivery—materials that could respond to changes in the immediate environment by altering their own physical properties.

Thanks to major advances in molecular engineering, scientists are now able to design materials so that they respond to specific kinds of external stimuli, including temperature, acidity, mechanical force, pressure, electrical potential, solvents, chemical agents, and even magnetic field, ionic strength, or certain wavelengths of light. The nature of the response can vary as well: Modifications of a material’s shape or surface characteristics, self-assembly, the formation of more intricate molecules, and transitions in physical state are all possible under the right conditions.

Different materials address different types of problems. One type turns into a gel when it warms up, then becomes a liquid again on cooling. Another material can be woven into a textile that can break and re-form chemical bonds in response to photostimulation, enabling it to act as a light sensor. These and other so-called smart materials are being developed right now in labs around the world. Such materials offer applications ranging from the delivery of therapeutics, tissue engineering, and bioseparation to intelligent optical systems, sensors, and coatings.

Collectively, the new smart materials fall into the class that chemists call polymers. The defining trait of polymers is that they consist of repeated chains of smaller molecules, like perfectly matched beads on a string. This versatile structure occurs throughout the natural world, forming the basis of materials as varied as rubber, beetle shells, and the silken threads of a spider’s web.

The beads in a polymer (known, in chemical terms, as monomers) are all exactly the same and are bonded to one another—an arrangement that gives polymers strength and flexibility. Moreover, many different monomers can be built up into polymers. These compounds have long been an important part of the chemist’s bag of tricks, but it required molecular-level engineering to make the polymers “smart,” allowing them to adapt in desirable ways to changes in the environment.

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