Multifunctional RNA Nanoparticles and Methods for Treating Cancer
T2018-230 Three-way junction nanoparticles for delivery of tamoxifen and other therapeutics directly to tumor cells.
Most breast cancers express estrogen receptor alpha (ER α) and antagonists of ER α drugs, such as tamoxifen, have been widely used for their treatment. Unfortunately, up to half of all ER α -positive tumors have intrinsic or acquired endocrine therapy resistance. Recent studies by the present investigators revealed that the ER coactivator Mediator Subunit 1 (MED1) plays a critical role in tamoxifen resistance through cross-talk with HER2.
A three-way junction nanoparticle specifically designed and self-assembled to target HER2-overexpressing human cancer by utilizing a HER2 RNA aptamer and to deliver MED1 siRNA to the cancer cells to effectively silence MED1 expression. The inventive nanoparticles specifically bind to HER2-overexpressing breast cancer cells, efficiently deplete MED1 expression and significantly decrease gene transcription. The extended arms of the 3 way motif are readily replaced with siRNAs and other RNA aptamers and the nanoparticles are ultra-compact with a very high Tm value. Proof-of-concept murine models were conducted and results showed that the nanoparticles targeted HER2 overexpressing breast cancer and silenced MED1 expression.
- Cancer therapeutic treatment for
- Treatment for those with primary or acquired resistance to anti-estrogenic agents
- Uniform nano-scale size
- Precise stoichiometry
- Stable and biocompatible
- High Tm value
- Non-toxic following systemic administration