Chemotherapy, the most widely accepted cancer treatment on the market, works by stopping or slowing the growth of cancer cells, which grow and divide rapidly. But, chemotherapy can harm healthy cells that divide quickly, causing a number of unwanted side effects. What if there was an anticancer drug that could attack – and kill – cancer cells without harming healthy cells and devoid of any side effects?

This is exactly what researchers at the Texas A&M Health Science Center Irma Lerma Rangel College of Pharmacy are testing, tiny drug vehicles, similar to “The Magic School Bus” in the popular children’s book series, that are capable of directly targeting cancerous cells in the body, bypassing healthy cells. The goal? Delivering the magic school bus – or cancer drug – directly into cancerous cells, killing them without damaging healthy cells.

Lin Zhu, Ph.D., assistant professor at the Texas A&M Rangel College of Pharmacy, is keen on improving drug effectiveness and minimizing side effects of cancer therapy drugs by using a particular enzyme that is unique to cancer cells and can be used as a target for cancer-specific delivery of anticancer drugs. The novel approach would allow scientists to program a drug nanocarrier (a tiny vehicle that exists on the nanometer scale and can significantly improve the physical, chemical and biological properties of the loaded drug molecules) that can specifically target the cancer-specific enzyme, efficiently enter the cancerous cells and then release the drug inside.

“The nanocarriers are like little missiles and the drug is not released until it enters the tumor,” Zhu said. “This allows high doses of toxic drugs to be given to only destroy the cancerous cells without negatively impacting healthy cells.”

To date, Zhu’s lab has overcome many challenges of current anticancer drugs, such as poor water solubility, insufficient tumor cell internalization, low tumor specificity, acquired drug resistance and severe side effects.

“Many drugs have poor water solubility and insufficient tumor cell internalization, causing low bioavailability, or a poor rate of absorption into cells,” Zhu said. “It is important to correct this, because even when you take a large amount of a drug, very little can be effectively utilized by the body.”

To increase the bioavailability, he is designing a drug-loaded nanocarrier, also known as nanomedicine, that can be directly engulfed by cancer cells. The drug is released internally and exhibits antitumor activity inside the cell. Another way he hopes to increase bioavailability is to modify the chemical structure of the drug in such a way to improve important properties such as solubility, without affecting its potency.

Even when the drug is dissolvable and enters the bloodstream, Zhu explained, you cannot be sure that the drug accumulates in the tumor. To remedy this, he looks for ways to impart the disease-specific properties to the medication. Zhu has designed nanocarriers with a protective shield and a tumor-sensitive linker between the nanocarrier’s core and shield. The tumor-specific enzyme, such as matrix metalloproteinase 2 (MMP2), acts like a pair of scissors, cutting away the linkers and exposing the unshielded nanocarriers to cancer cells. At the cellular level, the actions of the nanocarriers can be monitored and evaluated using florescent probes.

In addition to bioavailability and tumor specificity, Zhu researches ways to decrease drug resistance in cancer cells.

“After a patient uses a drug for a long time, the cancer cells develop resistance,” he said. This is similar to how bacteria react to antibiotics after prolonged use. He has two ways to increase the sensitivity to cancer drugs. Zhu mixes the drug into the nanomaterials, allowing it to be disguised in the carrier, and uses a combination of drugs within a nanocarrier to deliver a two-for-one punch into the cancerous cell.

The Controlled Release Society (CRS) recently recognized Zhu’s contributions to the field of drug delivery by awarding him the CRS T. Nagai Postdoctoral Research Achievement Award. This prestigious award recognized Zhu, who was a postdoctoral researcher, and his mentor, Vladimir P. Torchilin, Ph.D., distinguished professor at Northeastern University.

His research is a precursor to future medicines that will contribute to advancing patient care by improving specificity and reducing side effects.

Zhu has spent years researching targeted drug delivery. He has published more than 25 peer-reviewed articles in high impact journals, including Proceeding of the National Academy of Sciences of the United States of America, American Chemical Society (ACS) Nano, Angewandte Chemie, and Biomaterials; he has two patents, presented more than 14 presentations, and won several noteworthy awards in the fields of drug delivery and cancer research.

— Cheri Shipman

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