We know that, Arsenic trioxide is the inorganic compound with the formula As2O3. This commercially important oxide of arsenic is the main precursor to other arsenic compounds, including organoarsenic compounds. Approximately 50,000 tonnes are produced annually.Many applications are controversial given the high toxicity of arsenic compounds.
A Tiny Trojan Horse
The chemotherapy drug, arsenic trioxide, is packed into a very tiny Trojan horse called a nanobin. The nanobin consists of nano-size crystalline arsenic particles densely packed and encapsulated in a fat bubble. The fat bubble, a liposome, disguises the deadly cargo half a million drug molecules.
"You have to wallop the tumor with a significant dose of arsenic but at the same time prevent exposure to normal tissue from the drug," said O'Halloran. The fat bubble is hundreds of times smaller than the average human cell. It is the perfect size to stealthily slip through holes in the leaky blood vessels that rapidly grow to feed tumors. The local environment of the tumor is often slightly acid; it is this acid that causes the nanobin to release its drug cargo and deliver a highly effective dose of arsenic where it is needed.
The scientists show this approach to packaging and delivering the active drug has the desired effect on the tumor cells but prevents damage to ovarian tissue, follicles or eggs.
While the drug is gentle on fertility, it is ferocious on cancer. When tested against lymphoma, it was more potent than the drug in its traditional free form.
"The drug was designed to maximize its effectiveness but reduce fertotoxicity," said O'Halloran, also the Morrison Professor of Chemistry in the Weinberg College of Arts and Sciences at Northwestern. "Many cancer drugs cause sterilization, that's why the reproductive tract is really important to focus on in the new stages of drug design. Other body systems get better when people stop taking the drug, but fertility you can't recover."
Arsenic trioxide was approved a few years ago for treating some types of blood cancers such as leukemia in humans, but O'Halloran thinks the arsenic trioxide nanobins can be used against breast cancer and other solid tumors. In his previously published preclinical research, nanobins were effective in reducing tumor growth in triple-negative breast cancer, which often doesn't respond well to traditional chemotherapy and has a poor survival rate.
Quick Test For Fertility Toxicity
Woodruff was able to show early effects of the drug on fertility by using an in vitro follicle culture and a quick, simple new test she developed. She compared the fertotoxicity of the nanobin and free drug and found the nanobin was much less toxic to female fertility than the free drug in the experimental model.
"The system can be adapted very easily for any cancer drug under development to get an early peek under the tent,"said Woodruff, also the Thomas J. Watkins Memorial Professor of Obstetrics and Gynecology at Feinberg. "As this new drug goes forward in development, we can say this is a good drug for young female cancer patients who are concerned about fertility."
The information gained from the toxicity test will help inform the treatment decisions of oncologists and their young female cancer patients to improve their chances of creating a future family.
"They may prescribe less toxic drug regimens or refer them to specialists in fertility preservation," Woodruff said...
Ref : http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0058491
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