Release date: 2016-03-22
In a new study, researchers from the Houston Methodist Institute in the United States developed the first drug to successfully eliminate lung metastases in mice, which may trigger a revolution in metastatic triple-negative breast cancer. . The results of the relevant study were published online March 14, 2016 in the journal Nature Biotechnology, entitled "An injectable nanoparticle generator enhances delivery of cancer therapeutics".
Most cancer deaths are due to cancer cells metastasizing to the lungs and liver, and so far there is no cure. Existing anticancer drugs are unable to overcome the biological barriers in the body and the amount of drugs exposed to cancer cells is not sufficient, thus providing only limited benefits.
In this study, the researchers solved this problem by developing a drug that produces nanoparticles inside lung metastases in mice. They use doxorubicin (Dox), a cancer treatment drug that has been used by humans for decades, but has side effects on the heart. In addition, they also use the injectable nanoparticle generator (iNPG), which is made of nanoporous silicon material and can be naturally degraded in the body.
Specifically, they coupled Dox to poly-L-glutamic acid using a pH-sensitive cleavable linker and then loaded the drug polymer (pDox) formed into it. Inside the iNPG, it is assembled into iNPG-pDox. Upon release from iNPG, pDox spontaneously forms nano-sized particles in aqueous solution. After intravenous injection into mice, iNPG-pDox accumulates in the tumor, and pDox nanoparticles are released due to degradation of iNPG. The pDox nanoparticles can be taken up by the tumor cells into the interior of the cells. In tumor cells, pDox nanoparticles are transported to the area around the nucleus, and the acidity near the nucleus causes pDox to be cleaved, releasing Dox into the nucleus, thereby killing the tumor cells. This method can effectively prevent the drug discharge pump on the cell membrane from discharging the Dox.
Using this strategy to conduct studies in mice that have metastasized to the lungs of triple-negative breast cancer models, the researchers found that 50% of mice treated with this drug did not track metastatic disease after 8 months. This is equivalent to a patient with a metastatic disease that survives for about 24 years after receiving treatment.
Dr. Mauro Ferrari, President and CEO of the Houston Methodist Institute, said that due to the body's own defense mechanisms, most anticancer drugs are inhaled into healthy tissues, causing side effects, and only a small percentage of the drugs actually reach the tumor. It makes it less effective. This new treatment strategy allows the drug Dox to pass through multiple biological barriers in turn and ultimately to the nucleus of tumor cells. This active drug is released only inside the nucleus of metastatic tumor cells, thereby preventing multidrug resistance of cancer cells. This strategy effectively kills tumors in all mice and provides significant therapeutic benefit, including half of the mice being able to survive for long periods of time after treatment.
Ferrari said, "...we have invented a way to actually make nanoparticles inside cancer and release drug nanoparticles at the nuclear site. With iNPG, we can do standard chemotherapy drugs, vaccines, radiotherapy, but other nanometers. Things that particles can't do."
Ferrari said, “I never wanted to give too many promises to thousands of cancer patients looking for a cure, but the numbers are shocking. We are talking about changing the prospects for curing metastatic disease so that it is no longer Treated as a death sentence."
The researchers hope that the new drug will help clinicians cure lung metastases from other sites and may also cure primary lung cancer.
The Houston Methodist Institute has developed Good Manufacturing Practices (GMP) for the drug, plans to accelerate the study to obtain FDA approval, and plans to begin safety and efficacy studies in the human body in 2017.
Source: Bio Valley
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