Researchers from the University
of Notre Dame have engineered nanoparticles that show great promise for the
treatment of multiple myeloma (MM), an incurable cancer of the plasma cells in
bone marrow.
One of the difficulties doctors
face in treating MM comes from the fact that cancer cells of this type start to
develop resistance to the leading chemotherapeutic treatment, doxorubicin, when
they adhere to tissue in bone marrow.
“The nanoparticles we have
designed accomplish many things at once,” says Ba?ar Bilgiçer, assistant
professor of chemical and biomolecular engineering and chemistry and biochemistry,
and an investigator in Notre Dame’s Advanced Diagnostics and Therapeutics
(AD&T) initiative.
“First, they reduce the
development of resistance to doxorubicin. Second, they actually get the cancer
cells to actively consume the drug-loaded nanoparticles. Third, they reduce the
toxic effect the drug has on healthy organs.”
The nanoparticles are coated with
a special peptide that targets a specific receptor on the outside of multiple
myeloma cells. These receptors cause the cells to adhere to bone marrow tissue
and turn on the drug resistance mechanisms. But through the use of the newly
developed peptide, the nanoparticles are able to bind to the receptors instead
and prevent the cancer cells from adhering to the bone marrow in the first
place.
The particles also carry the
chemotherapeutic drug with them. When a particle attaches itself to an MM cell,
the cell rapidly takes up the nanoparticle, and only then is the drug released,
causing the DNA of cancer cell to break apart and the
cell to die.
“Our research 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.”
The group had to tackle three
important problems associated with all nanoparticle-based therapies, explains Jonathan
Ashley, one of the leading researchers of the project.
“There was some complex
bioengineering involved in developing the particles. We were able to precisely
control the number of drug and targeting elements on each nanoparticle, achieve
homogeneous nanoparticle size distribution and eliminate the batch-to-batch
variability in particle production.”
Before advancing to human
clinical trials, the team plans further research and testing to improve the
design of the nanoparticles and to find the optimum amount and combination of
chemotherapy drugs for this new treatment.
The research is published in Nature Blood Cancer Journal. It was supported by funding from
the Indiana Clinical and Translational Sciences Institute.
Source: University of Notre Dame
