Triplex Nanoparticles Against Cancer 1

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Submitted by João Conde, Nuria Oliva and Natalie Artzi of IMES/HST

Self-assembled RNA triple-helix hydrogel scaffold for microRNA modulation in the tumor microenvironment

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Artificial microRNAs can be used as a therapeutics to restore the natural tumor suppression activity or to inhibit mutated microRNAs involved in cancer progression. However, microRNA vast potential is limited by the lack of efficient delivery vehicle capable of delivering miRNAs to cancerous cells. Here, we created a stable woven self-assembled structure based on triplex-nanoparticles. RNA triple-helices comprising of a tumor suppressor microRNA and an anti-microRNA that inhibits a mutated tumoral microRNA were conjugated to dendrimer to allow for the formation of stable triplex- nanoparticles, which form an RNA triple-helix adhesive scaffold upon interaction with dextran aldehyde that coats the tumor. The device was further designed to report on the release of each microRNA by emitting two-color light and to report on tumor response following treatment.

In essence, we provide the body with armed soldiers to combat cancer, and with tools to inhibit the traitor soldiers that joined the cancer forces to abolish the body's retaliation mechanism. This vehicle was able to efficiently kill an aggressive breast cancer tumor in a mouse model and represents a game changer as we can now treat cancer locally and effectively while minimizing side effects and harnessing the body's natural weapons against cancer.