Injected Drug Forms Anti-Cancer Nanoparticles in Tumors

Mauro Ferrari (Houston Methodist Research Institute)

15 March 2016. Medical researchers developed a drug delivery technique that in lab mice forms anti-cancer nanoparticles inside metastatic tumors, promising much more potent cancer treatments. The team led by Mauro Ferrari and Haifa Shen at Houston Methodist Research Institute in Texas published its findings in yesterday’s (14 March) issue of Nature Biotechnology; paid subscription required.

Conventional cancer treatments, such as chemotherapy, often require large doses of powerful drugs, since much of the drug’s therapeutic chemicals are absorbed by healthy tissue, causing adverse side effects and leaving only a fraction of the drug to attack the tumor. To evade this obstacle, the team of medical researchers and materials scientists at Houston Methodist and other institutions designed a technology that suspends cancer drugs inside a protective coating that allows for the drug to form into therapeutic nanoparticles inside the tumor, before it can be diverted or absorbed elsewhere.

Ferrari, Shen, and colleagues developed its delivery techniques with the chemotherapy drug doxorubicin, which attacks and kills DNA in cancer cells and is used to treat a number of solid tumor and blood-related cancers. Doxorubicin, however, is associated with serious heart disorders, which sharply limits its utility to treating primary tumors, not those that metastasize, or spread to other parts of the body.

The team’s drug delivery technology combines nanoscale strands of doxorubicin with a natural biocompatible polymer used in drug delivery. Those strands are then suspended in biodegradable silicon and packaged in micrometer-sized particles, which are administered with intravenous injections.

Inside the body, the silicon degrades releasing the strands of doxorubicin and polymer, which accumulate at the site of tumors, where they are taken in by cancer cells. Inside cancer cells, surrounding the nuclei, the cells’ acidic nature breaks down the polymer holding the strands of doxorubicin, releasing the drug. The strands of doxorubicin then curl naturally into nanoscale drug particles, which attack and kill cancer cells from the inside.

The researchers tested the delivery technology in lab mice induced with metastatic breast cancer that spread to the animals’ lungs. The authors report that 8 months following the treatments, 40 to 50 percent of mice receiving the injections showed no evidence of metastasized cancer in the lungs. That period of time in mice, say the authors, is equivalent to about 24 years in humans.

Ferrari, who started work on nanoscale drug cancer delivery about 20 years ago, is president and CEO of Houston Methodist. “We invented a method,” says Ferrari in an institute statement, “that actually makes the nanoparticles inside the cancer and releases the drug particles at the site of the cellular nucleus. With this injectable nanoparticle generator, we were able to do what standard chemotherapy drugs, vaccines, radiation, and other nanoparticles have all failed to do.”

Houston Methodist says it established manufacturing facilities for these nanoparticle drugs, and plans to seek FDA approval for clinical trials next year. Ferrari tells more about nanoscale cancer drug delivery in the following video.

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