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Hunter-Killer Nanoparticle Bullets Target Tumors While Bypassing Healthy Tissue

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Credit: Tim Schoon/University of Iowa

Standard chemotherapy treatments involve infusing chemotherapeutic drugs into the blood stream. The drugs travel throughout the body seeking and attacking cells that are undergoing cell division or mitosis. Cancer cells are the favored targets for the drugs because they divide abnormally fast. However, chemotherapy drugs are indiscriminate killers. When a cell divides, the drugs attack it, and all the cells in the body divide. This is why chemotherapy is so debilitating for cancer patients. In the most extreme cases it’s a race to see if the drugs kill the cancer before the cancer or the drugs kill the patient.

Drug therapies that target malignant cells without attacking healthy tissue would solve this problem. A research team led by Aliasger K. Salem and Kareem Ebeid at the University of Iowa has developed a method for targeting malignant tumors using nanoparticles that carry a combination of chemotherapeutic drugs directly to the tumors without affecting healthy tissue. Their work was published in the journal Nature Nanotechnology.

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Creating hunter-killer nanoparticle bullets

Some cancers are resistant to chemotherapy because the tumor cells have a mutation called Loss of Function p53 that lets the cell repair itself before entering mitosis. The p53 mutation allows the cancer cell to survive without dividing. `A drug called nintedanib interferes with the action of the p53 mutation and forces the cell to divide. When it divides, it can be targeted by chemotherapeutic drugs.

The researchers paired nintedanib with paclitaxel a chemotherapy drug that is used to treat ovarian, breast, lung, cervical and pancreatic cancers among others. The two drugs in combination form an effective hunter-killer team targeting chemo-resistant forms of cancer. Nintedanib interferes with the action of the p53 mutation which causes the malignant cell to divide. When the cell divides, paclitaxel kills it.

The next step was devising a method for targeting tumors without attacking healthy cells. This is where the nanoparticles enter the picture. Fast-growing tumors create their own blood vessels so they can draw nutrients from the blood stream. The rapid growth of the tumor leads to the formation of flawed blood vessels that have small holes that are approximately 200 nanometeres in size. This leaves the tumor vulnerable to invasion by nanoparticles that are small enough to fit through the holes.

The researchers attached their nintedanib/paclitaxel hunter killers to nanoparticle bullets that were 175 nanometers or smaller. The bullets penetrated the tumors through the holes in the blood vessels and once inside, the hunter-killers went to work. The nanoparticle bullets bypassed healthy tissue because normal cell growth usually doesn’t result in flawed blood vessels with holes that allow the bullets to enter.

Credit: Wikimedia Commons

Testing the nanoparticle bullets

The research team tested their hunter-killer nanoparticles on mice with transplanted human type II endometrial cancer cells. The endometrium is a mucus membrane that lines the inside of the uterus, and endometrial cancer is the most widespread form of gynecological cancer in the US. Type II endometrial cancer is especially deadly. It grows quickly and spreads aggressively. Approximately 10% to 20% of endometrial cancers are type II, but they account for 40% of endometrial cancer deaths.

The hunter-killer nanoparticle bullets were tested against nanoparticles carrying paclitaxel without nintedanib, soluable paclitaxel in the bloodstream, and a saline infusion control.

The hunter-killer nanoparticles were the most effective treatment. Mice that received the hunter-killer bullets survived a median 51 days compared to 43 days for the next most effective treatment which was nanoparticles with paclitaxel alone. In addition, the mice treated with the hunter-killer nanoparticles maintained a stable body weight over the course of treatment, and showed no signs of cell death in tissue in the heart, lungs, liver, spleen or kidneys.

Credit: Wikimedia Commons

Conclusion

A therapy that targets tumors while leaving healthy tissue alone is the gold ring of cancer treatment research. The team at the University of Iowa is taking aim on that ring. The trick lies in attaching chemotherapeutic drugs to nanoparticle bullets that penetrate tumors and bypass healthy tissue.

The researchers focused on type II endometrial cancer, but they believe their approach can be applied to other types of cancer as well. All of the drugs they used have been approved for clinical use, and they hope to be able to begin testing with patients in the near future. The day may be coming when cancer patients don’t have to undergo the harsh treatment of chemotherapy infusions.

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