Polymersomes efficiently deliver siRNA to treat breast cancers in preclinical model

Small interfering RNAs or - siRNAs - hold promise to treat tumors, through their ability to specifically knock down oncogenes that promote tumor growth without the toxicity that accompanies chemotherapy. However, the siRNAs need a delivery vehicle to protect them from degradation and clearance on their journey through the bloodstream to the cancer tumor.

Eugenia Kharlampieva, Ph.D., and Eddy Yang, M.D., Ph.D., of the University of Alabama at Birmingham have demonstrated a 100-nanometer polymersome that safely and efficiently carries PARP1 siRNA to triple-negative breast cancer tumors in mice. There, the siRNA knocked down expression of the DNA repair enzyme PARP1, and remarkably, gave breast cancer-bearing mice a fourfold increase in survival.

PARP inhibitors have been successful in targeting tumors with defects in DNA repair and may modulate the tumor-immune microenvironment. However, due to bone marrow suppression, it has been challenging to combine many of the PARP inhibitors with chemotherapy. Specifically targeting PARP1 in the tumor may allow for novel combination treatments.

"To the best of our knowledge, our work represents the first example of biodegradable, non-ionic polymeric nanovesicles capable of efficiently encapsulating and delivering PARP1 siRNA to knock down PARP1 in vivo," they report in the journal ACS Applied Bio Materials. "Our study provides an advanced platform for developing precision-targeted therapeutic carriers, which could help develop effective drug delivery nanocarriers for breast cancer gene therapy."