Nanomedicines, the Guided Missiles for Biological Enemies Within

Advancements in nanomedicine are enabling treatments of everything from fungus to cancer to be targeted more precisely than ever before. Prof. Itai Benhar of Tel Aviv University is on the forefront of this defense system.

Nanomedicine, the process of applying medicine on a nanometric scale, is often described as the wave of the future, even though scientists have been working on it for four decades.

But there has been progress recently in the development of drug-carrying nanoparticles and making them even more efficient in how they distribute medicine. Essentially, the latest wrinkle in nanomedicine has turned those drug-filled particles into "guided missiles” aimed with deadly precision at their targeted cells.

“Targeted” is the key concept here because a primary goal of nanomedicine is to reduce collateral damage like the type caused by devastating treatments such as chemotherapy. Chemo may eliminate the disease but can cause terrible damage to the body in the process. The question of nanomedicine is how to get a chemical to zone in on specific problematic cells while leaving the good ones alone.

More than 20 different drug-carrying nano-treatments have been approved by the U.S. Food and Drugs Administration so far, taking the form of globules – big fat molecules containing toxic treatments within.

These globules behave like closed containers. They keep the toxic substances isolated from the blood stream and allow them to travel through the body until (hopefully) reaching their designated target, such as a cancerous growth. But they aren't very specific in their targeting, explains Prof. Itai Benhar from the Molecular Microbiology and Biotechnology Department at Tel Aviv University.

The older generation of liposomes, a form of artificial globules, was injected into the blood stream and disseminated throughout the body, explains Benhar, “eventually releasing the drug wherever they happened to be. The new systems will preferentially release the drug when they reach their target.”

Indeed, scientists around the world are working on the next generation of target-specific nanomedicines. None of these treatments have received FDA approval so far, and many of them are in an early experimental stage.

Fitting the key to the keyhole

Researchers in the field of targeted nanomedicine either chemically synthesize their drug-carrying systems or use natural biological processes and organisms to facilitate the guided delivery process. Benhar belongs to the latter group.

The main components in the delivery system that his team is developing are antibodies.

An antibody is a large protein that attacks foreign agents in the body. Antibodies are specific: a given antibody can identify a single agent – a specific strain of bacteria, a fungal spore, and so on. (In auto-immune diseases, antibodies mistakenly attack the patient's own body.)

When the antibody meets the offending target, it latches on. Then the antibody either destroys the target on its own or becomes a tag that notifies other body mechanisms of the invading object.

Most antibodies are quite alike, but their bonding sites, which allow them to latch onto invading bacteria or viruses, come in millions of variations. Thus each antibody fits only the specific targets that it’s programmed to attack.

Think of the antibody like a key and the bacteria, virus or fungus like a keyhole.

Benhar takes exploits this useful characteristic by turning antibodies into efficient guidance systems. He uses different antibodies for different medicines, each aimed at a different cell target (pathogenic bacteria, fungi, and cancer cells are a few examples).

While antibodies serve as Benhar's guiders, he uses viruses as his packaging systems.

Viruses are wondrously complex inventions of nature, but they have some helpful qualities. They are the quintessential parasite: incapable of reproducing on their own, each viral species infects very specific cells in very specific organisms. Thus, some scientists are trying to develop a guided delivery of drugs by harnessing virus’ innate talent for targeting. But unlike the antibodies that Benhar uses, scientists only know how to grow a few dozen viral strains. Thus as guided missiles, they can only accurately hit a few dozen specific cells.

Benhar, therefore, is trying something different by fusing the two ideas: He disarms a virus from its capacity to infect bacterial cells and turns it into a simple isolation package that can contain a drug and keep it from spreading in the body before it reaches its target. Once the drug is put into its package and the target-specifying antibody is attached to the virus, the drug-carrying system is ready to go.

“Today, when you come with an infection to the hospital, you'll be given a broad-spectrum antibiotic until the doctor figures out what you're suffering from," says Benhar. “You won’t get a selective antibiotic treatment until a few hours after your admittance, or even on the next day. But this so-called selective medicine isn't absolutely selective, since it targets several families of bacteria. By using antibodies as guidance systems, our development allows for the selective targeting of one certain species of bacteria."

This selective-targeting is of great benefit, since even narrow-spectrum antibiotics kill the good bacteria that inhabit our body on their way to killing the disease. More importantly, the new technique enables the existing arsenal of toxic drugs to be expanded, since selective targeting reduces the need to use significant amounts of these medicines. And as the pharmacological repertoire expands, the danger of bacterial resistance – a huge problem these days – diminishes.

"We've been developing our system for six or seven years, and it usually takes 20 years to develop a drug and get it out to the market," says Benhar. “At the end of the day our work is part of a greater field of experimentation where scientists constantly refer to each other’s works in search of the best solutions.

“We are all searching for different solutions to the same challenge,” he says, “and in the meantime developing a shared language. But there's no consensus at the moment as to what kind of system is going to come out of all this work.”