Nano delivery of cancer drugs increases effect by 5 times

Cancer drugs when delivered through a nanosponge can become five times more effective in reducing the tumour size than injected through vein through conventional means.

Researchers loaded commonly used anti-cancer drug paclitaxel (Taxol) into tiny sponges about the size of a virus. After attaching special chemical compounds that enable them to  bond on the surface of tumor cells, and then injecting them into the body and are released into the system.

These nano sponges circulate around the body until they encounter the surface of a tumor cell. Once they met with a cancer tumour cell, they stick on the surface and start releasing the drug in a controlled way.

“We call the material nanosponge, but it is really more like a three-dimensional network or scaffold,” according to Eva Harth, assistant professor of chemistry at Vanderbilt, who developed the nanosponge delivery system.

The nanosponges are made of polyester. The nanosponge is mixed in solution with small molecules that act like tiny grappling hooks to fasten different parts of the polymer together.

The drug molecules get stored into the spherically shaped particles filled with cavities.

Once in the system the biodegradable polyester breaks down gradually and releases the drug directly into the tumour cells.

The delivery of the drug through the nanosponge particles can be controlled.

Predictable release is one of the major advantages of this system compared to other nanoparticle delivery systems under development, according to Harth.

Normally, many other systems unload most of their drug in a rapid and uncontrollable fashion, once they reach their target. This usually makes it difficult to determine effective dosage levels.

The nanosponge particles can also be made larger or smaller by varying the proportion of cross-linker to polymer.

The study has shown that drug delivery systems work best when they are smaller than 100 nanometers.

The nanosponge particles used in the latest study were 50 nanometers in size.

The researchers are actively investigating the relationship between particle size and the effectiveness of these drug delivery systems.

Besides controlled delivery, targeted nanosponge delivery systems have several other advantages.

Since the cancer drug is delivered directly into the tumour, they do not cause damage to normal cells. This also makes the drug more effective.

The nanosponge particles are soluble in water. Nanosponge allows the use of hydrophobic anticancer drugs that do not dissolve readily in water.

Currently, hydrophobic anticancer drugs are mixed with another chemical, called an adjuvant reagent. This can reduces the efficacy of the drug and can have adverse side- effects.

The researchers have developed a simple, high-yield chemistry methods for making the nanosponge particles and for attaching the linkers, which are made from peptides.Peptides are small biological molecules built by amino acids.

The peptide used in the animal studies of the nanosponge was developed by the Hallahan Laboratory. The peptide used in the study is one that selectively binds to tumours that have been treated with radiation.

The researchers used the commonly used anticancer drug paclitaxel for the animal studies.

The nanosponge delivery of paclitaxel has been studied in two different tumor types – slow-growing human breast cancer and fast-acting mouse glioma.

In both cases the nanosponge delivery increased the death of cancer cells and delayed tumor growth in a manner superior to known chemotherapy approaches.

Now the researcher from the Vanderbilt University Medical Center and Alice E. van der Ende and Vasanth Sathiyakumar from Vanderbilt’s Department of Chemistry is planning to perform an experiment with repeated injections to see if the nanosponge system can stop and reverse tumor growth.

They are also planning to perform the more comprehensive toxicity studies on the nanosponge delivery system to assess its safety before taking it to human studies.

The research was supported by grants from the Department of Defense, National Science Foundation and National Institutes of Health.

The study was a collaboration between Harth’s Laboratory and that of Dennis E. Hallahan, a former professor of radiation oncology at Vanderbilt who is now at the Washington University School of Medicine.