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Shrinking tumors with an RNA triple-helix hydrogel glue

Brigham and Women's Hospital

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IMAGE: This is a high-resolution SEM image of RNA macrostructures embedded in the dextran-dendrimer hydrogel scaolds. view more

Credit: Natalie Artzi, BWH

Researchers at Brigham and Women's Hospital (BWH) have developed an efficient and effective delivery vehicle for gene therapy, and have used it to shrink tumors by nearly 90 percent in a pre-clinical model of triple-negative breast cancer. The new technique uses a hydrogel - a super-glue-like gel that spontaneously forms when two solutions mix - and self-assembled nanoparticles consisting of two microRNAs that suppress and target tumor tissue. This platform can be injected locally, allowing the researchers to increase dosage at the site of the tumor while decreasing the risk of the therapy accumulating in the kidneys, liver or other organs. In mouse models, the adhesive containing self-assembled nanoparticles injected using this approach has been far more potent, selective and specific to tumor cells than conventional chemotherapeutic drugs and have lengthened survival time.

"Cancer is usually viewed as a systemic disease requiring systemic therapy but here we show that local therapy is actually very potent," said senior author Natalie Artzi, PhD, a researcher in the BWH Department of Medicine, Biomedical Engineering Division, and the Harvard-MIT Division for Health Sciences and Technology. "The results are outstanding and demonstrate the power of local, sustained delivery, and the promise of gene therapy in cancer treatment."

The researchers note that this approach can be used to deliver other combinations of microRNAs or other types of genetic material, including antisense DNA or small interfering RNA, to treat a wide-range of diseases. As a next step, the team will test the technique for biocompatibility and efficacy in larger animal models and will scale up their platform to screen for additional potentially therapeutic microRNAs and cancer therapies that can be combined to improve treatment.

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