RNA nanoparticles offer a dual effect against prostate tumors

RNA nanoparticles offer a dual effect against prostate tumors

Yang Zhang, PhD, and Jinjun Shi, PhD, both of the Center for Nanomedicine and the Division of Anesthesiology, Perioperative and Pain Medicine at Brigham and Women's Hospital, are co-senior authors of a paper, "Lipid Nanoparticle Delivery," published in ACS Nanoscience Au. of mRNA and siRNA to simultaneously restore the tumor suppressor and inhibit the tumorigenic driver in prostate cancer.”

How would you summarize your study for a lay audience?

Most cancers arise when there is an imbalance between cell growth and cell inhibition, causing cells to grow rapidly and form tumors in the body. For example, advanced prostate cancer (PCa) is often associated with changes in the activity of a tumor suppressor called phosphatase and tensin homolog on chromosome 10 (PTEN) and a widely studied protumorigenic transcription factor called androgen receptor (AR). However, there are no therapies to simultaneously correct tumor growth and restore tumor suppression in patients with PCa.

Using a novel RNA-based approach, we sought to restore this balance in cancer therapies for patients with PCa. This approach has been successful in preclinical models and promises to suppress tumor growth in patients.

What question did you investigate?

We hypothesized that the simultaneous use of mRNA and siRNA in patients with PCa could restore tumor suppressors and inhibit tumor growth drivers such as PTEN and AR, respectively.

What methods did you use?

We used lipid nanoparticles to deliver mRNA and siRNA to human PCa cells to evaluate the ability of our technique to both restore the lost PTEN and silence the overexpressed AR.

What did you find?

We saw a potent, combined antitumor effect when the mRNA and siRNA nanoparticles were administered to PCa cells.

What are the effects?

Our strategy could also be applied to other tumor growth drivers and tumor suppressors in prostate cancer and other cancers such as breast cancer, non-small cell lung cancer and hepatocellular carcinoma. If we carefully select specific routes of attack that target tumor growth and suppression, this strategy holds the potential for developing more effective treatments for many types of cancer.

What are the next steps?

We will extend this approach to evaluate its effectiveness in other cancer types. We also plan to further explore the biological mechanisms underlying the combined effects we observed, which could lead to the discovery of new, effective therapeutic targets for PCa.

Sources: