Multiple myeloma (MM) is a cancer of the plasma cells in bone marrow. Researchers from the University of Notre Dame’s Advanced Diagnostics and Therapeutics initiative have engineered nanoparticles that could prove key in treatment for this incurable cancer.
Because its cancer cells can develop resistance to doxorubicin, a common chemotherapeutic regimen, when they attach to tissue in bone marrow, MM is incredibly difficult to treat. Jonathan Ashley, noted several main issues related to nanoparticle therapies and what the researchers were able to accomplish. “The development of these nanoparticles included some intricate bioengineering work. The team was able to control the drug and targeting elements present on each nanoparticle, eliminated the batch-to-batch variability during the production of particle, and achieved homogeneous nanoparticle size distribution.”
The nanoparticles work by targeting specific receptors that the MM cells have on their outside. These receptors make the cells resistant to traditional cancer treatments by enabling drug-resistance mechanisms when the MM cells hit bone marrow cells. The nanoparticles have been engineered with a peptide coating that can target a specific receptor and prevent the cancer cells from reaching the bone marrow at all. In addition to protecting the bone marrow cells from the MM cells, the nanoparticles carry the treatment with them. When a particle attaches itself to an MM cell, the chemotherapeutic drug is released, causing the DNA of the MM cell to be destroyed when it is broken apart from the inside. With this new development, the nanoparticles connect to the receptors; and thus, stop cancer cells from connecting to the bone marrow.
The researchers at Notre Dame were multi-focused. Basar Bilgiçer, an investigator in Advanced Diagnostics and Therapeutics (AD&T) initiative of Notre Dame and also an assistant professor of chemistry and biochemistry and chemical and biomolecular engineering, said that the engineered nanoparticles can “achieve many things at once. Firstly, the nanoparticles prevent the cancer cells from developing resistance to doxorubicin. Secondly, they cause the cancer cells to actively take up the drug-loaded nanoparticles. Thirdly, they reduce the toxicity of the drug on healthy organs.”
Research conducted on mice shows that “the nanoparticle formulation reduces the toxic effect doxorubicin has on other tissues, such as the kidneys and liver,” adds Tanyel Kiziltepe, a research assistant professor with the Department of Chemical and Biomolecular Engineering and AD&T. “We believe further research will show that the heart is less affected as well. This could greatly reduce the harmful side-effects of this chemotherapy.” Doxorubicin is incredibly effective in destroying most cancer cells, but has an equally destructive influence on other tissues as well.
Not ready for human clinical trials at this point, Ashley reports that the team at Notre Dame must first work to balance the amount and combination of the chemotherapeutic drugs. The design may also be improved. Researchers believe the nanoparticles can also be engineered to target other treatment-resistant cancers as well.