Therapeutic Outcome in Triple Negative Breast Cancer Achieved Through Multitarget Antagonization of miRNAs

Strategic Insights -

Triple negative breast cancer (TNBC) is a highly aggressive form of breast cancer characterized by the absence of estrogen, progesterone, and HER2 receptors, making it difficult to treat. Researchers at Stanford University have made a breakthrough in the development of a new therapeutic approach for TNBC by simultaneously antagonizing miR-21-induced antiapoptosis and miR-10b-induced metastasis using antisense-miR-21-PS and antisense-miR-10b-PS delivered by polymer nanoparticles (NPs).

Key Takeaways:

  • The researchers synthesized antisense-miR-21 and antisense-miR-10b loaded PLGA-b-PEG polymer NPs and evaluated their cellular uptake, serum stability, release profile, and subsequent synchronous blocking of endogenous miR-21 and miR-10b function in TNBC cells in culture and tumor xenografts in living animals using molecular imaging.
  • The multitarget antagonization of endogenous miRNAs showed a substantial reduction in tumor growth at a very low dose of 0.15 mg/kg in mice treated with targeted delivery of antisense-miR-21-antisense-miR-10b coloaded uPAR-targeted polymer NPs.
  • The treatment demonstrated a 40% reduction in tumor growth compared to scramble peptide conjugated NPs-treated mice, and a significant reduction in tumor growth compared to control NPs-treated mice.
  • This new therapeutic approach has the potential to become an efficient strategy for targeting metastasis and antiapoptosis in the treatment of metastatic cancer.
  • The researchers have made significant progress in the development of a new therapeutic option for TNBC, which may improve the prognosis for patients with this aggressive form of breast cancer.

Statistics:

  • 40% tumor growth reduction in mice treated with antisense-miR-21 and antisense-miR-10b coloaded uPAR-targeted polymer NPs compared to scramble peptide conjugated NPs-treated mice.
  • 0.15 mg/kg is the dose at which substantial tumor growth reduction was observed in mice treated with targeted delivery of antisense-miR-21 and antisense-miR-10b coloaded uPAR-targeted polymer NPs.
  • The research was published in ACS Nano (2015;9(3):2290-2302).

Sources:

  • ACS Nano, 2015;9(3):2290-2302
  • Amer Chemical Soc, 1155 16TH St, NW, Washington, DC 20036, USA
  • R. Devulapally, Stanford University, Sch Med, Dept. of Radiol, Mol Imaging Program StanfordBioX Program, Palo Alto, CA 94304, United States.