Scientists develop experimental 'nano-chemo' particle to treat bladder cancer

October 12, 2017
Johns Hopkins scientists develop experimental 'nano-chemo' particle to treat bladder cancer
Florescent red nanoparticles distributed throughout blue-dyed bladder tissue in mice. Credit: Umara Afzal and Abhijit Date

Working with mice and rats, Johns Hopkins researchers have developed a way to successfully deliver nano-sized, platinum-based chemotherapy drugs to treat a form of bladder cancer called nonmuscle-invasive that is found in the lining of the organ and has not invaded deeper into bladder tissue. The tiny drug-infused particles, they say, potentially offer a less toxic clinical alternative to standard chemotherapy delivered intravenously or through a catheter inserted into the bladder.

The team of investigators from the Brady Urological Institute and the Center for Nanomedicine at Johns Hopkins, engineered the nanoparticles from biologically compatible materials, such as polyaspartic acid, and coordinated them with molecules of the chemotherapy cisplatin, considered a first-line treatment for human bladder cancers that have spread through the organ's inner lining into its muscle tissue.

In a series of laboratory tests with mice and a rat model of bladder cancer, the scientists found that the nanoparticles, when administered through a catheter directly to the bladder, reduced the proliferation of cancer cells without leaching into to the bloodstream, which takes the drug's toxicity and other side effects to the whole body. The work was published online Aug. 14 in the journal Clinical Cancer Research.

"We were really excited by these results," says Max Kates, M.D., a urology chief resident at The Johns Hopkins Hospital and lead author of the study. "We have been interested in developing new therapies for bladder cancer to allow patients who have early stage disease but who don't respond to first line treatment to keep their bladders." First line treatment consists of the drug BCG or bacillus calmette-guerin. If it fails, such patients typically have a cystectomy, surgical removal of the bladder.

Previous studies giving cisplatin in its customary, non-nano-sized state, through a catheter inserted into the bladder, have found it to be too toxic, leaching through the bladder to the bloodstream. Intravenous forms of cisplatin have not been considered for patients with early stage disease because of potential side effects such as acute kidney injury.

For the current study, Johns Hopkins scientists Abhijit Date, Ph.D., and Laura Ensign, Ph.D., led the design of the nano-chemoparticles to increase absorption of the drug into the bladder without being diluted by urine production and to stay within the bladder to better attack tumors. The scientists first delivered the drug nanoparticles or regular cisplatin to mice, finding that the nanoparticles were more than 20 times better absorbed by the animals' bladders four hours after administration and had at least two to three times less systemic absorption than regular drug.

Next, they administered either the drug nanoparticles or regular cisplatin to the bladders of mice via a catheter once a week for three weeks, then studied blood and bladder tissue samples, finding detectable levels of the drug's platinum content in the blood of animals treated with regular cisplatin but not in those treated with the drug nanoparticles.

Last, they gave both drugs to rats with cancer. The nanoparticles provided a six-fold increase in drug concentration in the animals' bladders one hour after treatment, and 10-fold more drug was retained four hours after treatment, compared with rats that received regular cisplatin. No rats treated with the drug nanoparticles had signs of high-grade tumors 16 weeks after treatment, whereas at least 20 percent of rats treated with typical cisplatin and half of the rats given no treatment had evidence of high-grade tumors by this time.

"This study represents a significant improvement for intravesical platinum drug delivery that we believe is highly applicable for patients with nonmuscle-invasive ," says senior study author Trinity J. Bivalacqua, M.D., Ph.D., director of urologic oncology at the Brady Urological Institute at Johns Hopkins, deputy director of the Johns Hopkins Greenberg Bladder Cancer Institute and the R. Christian B. Evenson Professor of Urology and Oncology at the Johns Hopkins University School of Medicine and Kimmel Cancer Center. "Following further analyses, we hope to initiate early phase clinical trials to evaluate the safety and efficacy of this treatment for patients."

Bladder is the seventh most common malignancy worldwide, affecting about 1.3 million people. Approximately 70 percent of patients are diagnosed at the non-muscle invasive stage.

Explore further: Drug created from malaria parasite shows promise as bladder cancer treatment

More information: Clinical Cancer Research (2017). DOI: 10.1158/1078-0432 , http://clincancerres.aacrjournals.org/content/early/2017/08/12/1078-0432.CCR-17-1082

Related Stories

Drug created from malaria parasite shows promise as bladder cancer treatment

April 20, 2017
A drug created from a malaria protein stopped tumour growth of chemotherapy-resistant bladder cancer, offering hope for cancer patients not responding to standard treatments.

New bladder cancer therapy to start clinical trials

June 27, 2017
An experimental treatment for bladder cancer will move into an early phase clinical trial under an agreement signed today (Monday) between Cancer Research UK and Cancer Research Technology (CRT), the charity's commercial ...

Simple post-surgery step significantly reduces bladder cancer recurrence

May 15, 2017
It's just one step. Flushing the bladder with a common chemotherapy drug after a cancerous tumor is surgically removed reduces the chances of that cancer returning. Canadian and European clinical trials have proven this true ...

Heating chemotherapy drugs may improve bladder cancer treatment

May 17, 2016
Scientists have found that heating the chemotherapy drug mitomycin-C prior to using it for treating bladder cancer may radically improve its efficacy. The findings, published in the International Journal of Hyperthermia, ...

Immune cells the missing ingredient in new bladder cancer treatment

July 24, 2017
New research offers a possible explanation for why a new type of cancer treatment hasn't been working as expected against bladder cancer.

Cold medicine could stop cancer spread

October 17, 2016
Hokkaido University researchers have discovered that a nonsteroid anti-inflammatory drug used for treating colds suppresses the spread of bladder cancers and reduces their chemoresistance in mice, raising hopes of a future ...

Recommended for you

Researchers develop test that can diagnose two cancer types

December 12, 2017
A blood test using infrared spectroscopy can be used to diagnose two types of cancer, lymphoma and melanoma, according to a study led by Georgia State University.

Atoh1, a potential Achilles' heel of Sonic Hedgehog medulloblastoma

December 12, 2017
Medulloblastoma is the most common type of solid brain tumor in children. Current treatments offer limited success and may leave patients with severe neurological side effects, including psychiatric disorders, growth retardation ...

Cancer-causing mutation suppresses immune system around tumours

December 12, 2017
Mutations in 'Ras' genes, which drive 25% of human cancers by causing tumour cells to grow, multiply and spread, can also protect cancer cells from the immune system, finds a new study from the Francis Crick Institute and ...

Drug suppresses spread of breast cancer caused by stem-like cells

December 12, 2017
Rare stem-like tumor cells play a critical role in the spread of breast cancer, but a vulnerability in the pathway that powers them offers a strategy to target these cells using existing drugs before metastatic disease occurs, ...

MRI scans predict patients' ability to fight the spread of cancer

December 12, 2017
A simple, non-invasive procedure that can indicate how long patients with cancer that has spread to the brain might survive and whether they are likely to respond to immunotherapy has been developed by researchers in Liverpool.

Scientists discover possible master switch for programming cancer immunotherapy

December 11, 2017
During infection or tumor growth, a type of specialized white blood cells called CD8+ T cells rapidly multiply within the spleen and lymph nodes and acquire the ability to kill diseased cells. Some of these killer T cells ...

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.