October is Breast Cancer Awareness Month, a good time to remember that breast cancer is one of the most common cancers in women. Despite breakthroughs in diagnosis and treatment, about 1,000 Israeli women – 15% of them under the age of 50 – die of the disease in an average year. Worldwide, some 685,000 women annual are victims of breast cancer.
Researchers at the Technion-Israel Institute of Technology in Haifa have just published findings in the journal Science Advances that support the efficacy of a new technology that they developed – treatment of breast cancer by anesthesia of the nervous system around the tumor. The treatment in laboratory mice not only inhibited tumor growth but also prevented metastasis (spreading) to other organs.
The study, entitled “Targeting neurons in the tumor microenvironment with bupivacaine nanoparticles reduces breast cancer progression and metastases,” was led by Prof. Avi Schroeder and doctoral. student Maya Kaduri of the Technion’s Wolfson Faculty of Chemical Engineering. The research was conducted in cooperation with the Faculty of Medicine at Hebrew University of Jerusalem and the Institute of Pathology at the Tel Aviv Sourasky Medical Center.
“Neurons within the tumor microenvironment promote cancer progression; thus, their local targeting has potential clinical benefits. We designed PEGylated lipid nanoparticles loaded with a non-opioid analgesic, bupivacaine, to target neurons within breast cancer tumors and suppress nerve-to-cancer cross-talk,” they wrote.
Schroeder has years of experience in developing innovative cancer treatments, including breast cancer and specifically triple-negative breast cancer – an aggressive cancer characterized by rapid cell division with a higher risk of metastasis. Technologies developed in his lab include novel methods for encapsulating drug molecules in nanoparticles that transport the drug to the tumor and release it inside, without damaging healthy tissue.
The researchers found that cancer cells have a reciprocal relationship with the nerve cells around them; the cancer cells stimulate infiltration of nerve cells into the tumor, and this stimulates cancer cell proliferation, growth and migration. In other words, the cancer cells recruit the nerve cells for their purposes.
Based on these findings, the researchers developed a treatment that targets the tumor through the nerve cells. This treatment is based on injecting nanoparticles containing anesthetic into the bloodstream. The nanoparticles travel through the bloodstream toward the tumor, accumulate around the nerve cells in the cancerous tissue and paralyze the local nerves and communication between the nerve cells and the cancer cells. The result: significant inhibition of tumor development and of metastasis to the lungs, brain and bone marrow.
The nanoparticles simulate the cell membrane and are coated with special polymers that disguise them from the immune system and enable a long circulation time in the bloodstream. Each such particle, which is around 100 nanometer in diameter, contains the anesthetic.
“We know how to create the exact size of particles needed, and that is critical because it’s the key to penetrating the tumor,” explained Kaduri. “Tumors stimulate increased formation of new blood vessels around them, so that they receive oxygen and nutrients, but the structure of these blood vessels is damaged and contains nano-sized holes that enable penetration of nanoparticles. The cancerous tissue is characterized by poor lymphatic drainage, which further increases accumulation of the particles in the tissue. Therefore, the anesthetizing particles we developed move through the bloodstream without penetrating healthy tissue.”
Only when they reach the damaged blood vessels of the tumor do they leak out, accumulate around the nerve cells of the cancerous tissue and disconnect them from the cancer cells, she continued. “The fact that this is a very focused and precise treatment enables us to insert significant amounts of anesthetic into the body because there is no fear that it will harm healthy and vital areas of the nervous system.”
In experiments on cancer cell cultures and in treatment of mice, the new technology inhibited not only tumor development but also metastasis. The researchers estimate these findings could be relevant for treatment of breast cancer in humans.