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Nanoparticles Deliver Therapeutics to Diseased Livers

2016-01-28
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    UT Southwestern Medical Center chemists have successfully used synthetic nanoparticles to deliver tumor-suppressing therapies to diseased livers with cancer, an important hurdle scientists have been struggling to conquer.

 

    The dendrimer nanoparticles were able to exert their effect without further damaging the liver or neighboring tissue, according to the researchers who published their findings (“Modular degradable dendrimers enable small RNAs to extend survival in an aggressive liver cancer model”) in the Proceedings of the National Academy of Sciences.


“We found that efficacy required a combination of a small-RNA drug that can suppress cancer growth and the carrier, thereby solving a critical issue in treating aggressive liver cancer and providing a guide for future drug development,” said Daniel Siegwart, Ph.D., assistant professor of biochemistry and with the Harold C. Simmons Comprehensive Cancer Center.

 

    The recent failure of five Phase III human clinical trials of small-molecule drugs to treat hepatocellular carcinoma prompted the authors to develop non-toxic carriers and explore micro RNA (miRNA) therapies as a promising alternative. miRNAs can function as natural tumor suppressors but require delivery strategies to transport these large anionic drugs into cells. To date, no existing carrier has been able to provide effective delivery to late-stage liver cancer without amplified toxicity, which negates the desired effect.

 

    To address this problem, UTSW scientists chemically synthesized more than 1,500 different types of nanoparticles, which allowed discovery of lead compounds that could function in the heavily compromised cancerous liver. Synthetic nanoscale dendrimers provided an opportunity to screen different combinations of chemical groups, physical properties, and molecular size, Dr. Siegwart said. This approach led to the identification of dendrimers to deliver miRNA to late-stage liver tumors with low liver toxicity.

 

    According to the researchers the study, conducted in genetic mouse models with a highly aggressive form of liver cancer, demonstrated that the miRNA nanoparticles inhibited tumor growth and dramatically extended survival.

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