Researchers develop new drug delivery system for bladder cancer using nanoparticles

October 25, 2012

A team of UC Davis scientists has shown in experimental mouse models that a new drug delivery system allows for administration of three times the maximum tolerated dose of a standard drug therapy for advanced bladder cancer, leading to more effective cancer control without increasing toxicity.

The delivery system consists of specially designed nanoparticles that home in on while carrying the anti-cancer drug paclitaxel. The same delivery system also was successfully used to carry a dye that lights up on imaging studies, making it potentially useful for diagnostic purposes. The findings are published today in the journal Nanomedicine.

"We have developed a novel, multifunctional nanotherapeutics platform that can selectively and efficiently deliver both diagnostic and to bladder tumors," said Chong-Xian Pan, principal investigator of the study and associate professor of hematology and oncology at UC Davis. "Our results support its potential to be used for both diagnostic and therapeutic applications for advanced bladder cancer."

Cancer of the bladder usually develops in the cells of the inner lining of the bladder. Survival rates are high if the disease is caught early, but it remains difficult to treat in advanced stages ― when the tumor has grown outside of the bladder or metastasized to distant sites. It is the fourth most common cancer in men; it occurs less frequently in women.

Paclitaxel is a drug used to treat advanced bladder cancer and other cancers, but it is associated with serious safety concerns. It can be toxic to bone marrow, leading to reduced levels of red and , putting patients at risk of infection. In addition, because the drug is not readily soluble in blood, it is typically dissolved in castor oil, which has caused severe ― and sometimes fatal ― allergic reactions.

The used in this study makes use of nanoparticles called micelles developed by Kit Lam, professor and chair of the UC Davis Department of Biochemistry and Molecular Medicine and a co-author of the article. Micelles are aggregates of soap-like molecules that naturally form a tiny spherical particle with a hollow center. The researchers incorporated specific targeting molecules ― called ligands ― into the micelle structure. These ligands, developed by UC Davis researchers, were successfully shown in earlier studies to preferentially bind to bladder cancer cells derived from dogs and humans.

In addition to the cancer-targeting ligands, the micelles were loaded with paclitaxel. Experiments were run on mice receiving different dosages of the drug: the standard dosage currently used for therapy, and another dosage three times that amount. Mice receiving the standard dosage had significantly less tumor growth and longer overall survival compared to control mice who received a saline solution instead of drug therapy. Mice that received the high dosage took the longest time to develop a tumor and had the most days of tumor control. They also had nearly three times longer survival than mice that received drug therapy in the conventional way ― without the use of the nanoparticle delivery system. The high dosage conferred few side effects and no deaths.

"The prognosis for advanced bladder cancer has not changed for three decades," said Pan. "Our findings have the potential to significantly improve outcomes."

Mice used in the experiments were specially injected with human bladder cancer cells obtained directly from patients with the disease. This technique is believed to make the study results more clinically relevant than the more common method of using cancer cell lines that have been maintained in laboratories for research purposes for long periods of time. According to the study authors, the transplanted tumors were highly aggressive cancers.

In other experiments, the researchers loaded the bladder-cancer-homing micelles with a fluorescent imaging dye instead of . The imaging results proved that the micelles were targeting the cells and indicated that the technique may have clinical applications for diagnosis and monitoring therapy.

"These research findings are extremely exciting on many levels," said Ralph deVere White, director of the UC Davis Comprehensive Cancer Center and a study author. "We have very promising results using a novel technology that may offer a new approach to treating a variety of very difficult-to-treat cancers. I look forward to seeing this approach move forward in clinical trials."

Explore further: Like prostate cancer, bladder cancer patients may benefit from anti-androgen therapy

Related Stories

Like prostate cancer, bladder cancer patients may benefit from anti-androgen therapy

September 24, 2012
Bladder cancer patients whose tumors express high levels of the protein CD24 have worse prognoses than patients with lower CD24. A University of Colorado Cancer Center study published today in the Proceedings of the National ...

Tapping the body's own defenses, researchers look to cutting-edge gene therapy for bladder cancer

January 10, 2012
Bladder cancer, most frequently caused by smoking and exposure to carcinogens in the workplace, is one of the top 10 most common forms of cancer in men and women in the U.S. More than 70 percent of bladder cancers are diagnosed ...

New made-in-Canada therapy for bladder cancer shows promising results

May 24, 2011
Clinical trials for a new bladder cancer therapy show promising interim results. Lead researcher Alvaro Morales says that the breakthrough using the drug Urocidin follows thirty years of his research in this important area.

Recommended for you

Researchers repurpose immune-activating cytokine to fight breast cancer

December 18, 2017
The most lethal form of breast cancer could have a new treatment option, according to new research out of the Case Comprehensive Cancer Center at Case Western Reserve University School of Medicine. In the Proceedings of the ...

What does hair loss have to teach us about cancer metastasis?

December 15, 2017
Understanding how cancer cells are able to metastasize—migrate from the primary tumor to distant sites in the body—and developing therapies to inhibit this process are the focus of many laboratories around the country. ...

Cancer immunotherapy may work better in patients with specific genes

December 15, 2017
Cancer cells arise when DNA is mutated, and these cells should be recognized as "foreign" by the immune system. However, cancer cells have found ways to evade detection by the immune system.

Scientists pinpoint gene to blame for poorer survival rate in early-onset breast cancer patients

December 15, 2017
A new study led by scientists at the University of Southampton has found that inherited variation in a particular gene may be to blame for the lower survival rate of patients diagnosed with early-onset breast cancer.

Scientists unlock structure of mTOR, a key cancer cell signaling protein

December 14, 2017
Researchers in the Sloan Kettering Institute have solved the structure of an important signaling molecule in cancer cells. They used a new technology called cryo-EM to visualize the structure in three dimensions. The detailed ...

'Bet hedging' explains the efficacy of many combination cancer therapies

December 14, 2017
The efficacy of many FDA-approved cancer drug combinations is not due to synergistic interactions between drugs, but rather to a form of "bet hedging," according to a new study published by Harvard Medical School researchers ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.