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Researchers exploring the use of nanoparticles to treat and reduce the size of deep-seated cancer cells have found their method to be effective. Using nanoparticles as part of a specialized delivery system, the team focused the treatment on a rare bone cancer (chondrosarcoma) in laboratory mice. What they witnessed was a reduction in the tumor size as well as an extended life-span in the mice models being tested.
Published in the ACCR journal, Molecular Cancer Therapeutics, the team outlines the complicated nature of the process, stating, “one challenge to (drug) delivery in chondrosarcoma is the negatively charged proteoglycan-rich extracellular matrix that needs to be penetrated to reach the tumor cells.” Leading the research, Richard Terek, chief of musculoskeletal oncology at Rhode Island Hospital, and Qian Chen, professor at Brown and director of the NIH-funded Center of Biomedical Research Excellence in Skeletal Health and Repair at Rhode Island Hospital, highlighted the need for an FDA approved treatment for chondrosarcoma which is made up of a notoriously complex set of a cancer cells.
Terek and Chen worked together to create a nanopiece delivery platform that could permeate the chondrosarcoma matrix. By penetrating the complex make-up of the cancer cells the technique could ensure that that drug treatments are delivered to the requisite tumor tissues and cells.
We develop nanomaterial (that) we call nanopieces and we found that it can deliver nucleic acid therapeutics to tissues that normally are very difficult to be penetrated.
Qian Chen, Professor Brown University and Director, The NIH-funded Center of Biomedical Research Excellence in Skeletal Health and Repair, Rhode Island Hospital
To better understand and advance the technique, the researchers analyzed the biological growth and spread of chondrosarcoma and formation of miRNA, short sequences of 21-nucleotide single stranded molecules. These strands of miRNA are usually overly-abundant in chondrosarcoma cells and accelerate cancer formation by impacting the surrounding genes in the cancer pathway.
Over the past 10 years, Terek has been working on a detection process that can identify miRNA present in chondrosarcoma formation as an oncogenic, or cancer-causing agent.
That process involved microarray analysis of primary human tumor tissues. We used a variety of screening techniques to identify which miRNA were overexpressed in tumors.
Richard Terek, Chief, Musculoskeletal Oncology, Rhode Island Hospital
Therefore, by identifying the miRNA sequence and synthesizing a set of opposing RNA sequences the damaging oncogenic effects can be inhibited. This part of the process requires delivering the synthesized RNA nucleotides using the nanoparticles. “What we do in the lab is … formulate this nanomaterial specifically for penetrating into the matrix,” Chen said.
Chen has also had previous success with nanoparticle-based therapies in studies focusing on diseases such as rheumatoid arthritis. Furthermore, Chen’s lab team has received funding from the National Institutes of Health to develop a nanopiece delivery system that can be used in the treatment of Alzheimer’s disease.
Additionally, another recent paper published in Proceedings of the National Academy of Sciences (PNAS), has made progress in the use of nanoparticles in radiation therapy. Leading that study, Wei Chen, Professor of Physics at the University of Texas Arlington, said, “Traditional nanoparticles used for photodynamic therapy can only be activated by light that is not highly penetrating, meaning we're limited with how deep we can go to target tumors.” Wei Chen has also been working on developing nanoparticle treatment for some time and has collaborated with Leon Cooper, a Nobel Prize laureate from Brown University.
Terek and Chen’s research also has the potential to be combined with other cancer drug therapies and could usher in the use of conventional therapies, such as chemotherapy, for cancers that would otherwise demonstrate a resistance to such treatments.
While nanoparticle therapy shows significant promise in order for progress to continue and treatments succeed, pharmaceutical companies, biotech companies, and other investors and collaborators must commit their time and award funding to such projects. Brown University and Lifespan have set up a startup called NanoDe to continue research and development on the project. Chen said, “As far as moving it into the clinic, that’s always a big hurdle.”
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