Chitosan nanoparticle-delivered siRNA reduces CXCR4 expression and sensitizes breast cancer cells to cisplatin

Abstract

Chemokine (C-X-C motif) receptor 4 (CXCR4) has been reported as a poor prognostic biomarker in human breast cancers, and has been suggested as a promising therapeutic target of breast cancer treatment. The present study aims to investigate the delivery efficiency of siRNA by chitosan into breast cancer cells, and then to examine the regulatory role by chitosan nanoparticle-delivered siRNA on CXCR4 expression and on the chemosensitivity of breast cancer cells. Our results demonstrated that the siRNA could be capsuled by chitosan into nanoparticles with a diameter of 80–110 nm, and with a zeta potential of 20–50 mV. The chitosan nanoparticle delivered siRNA efficiently into breast cancer MCF-7 cells significantly reduced the expression of CXCR4 in both mRNA and protein levels. Moreover, the reduced CXCR4 by chitosan nanoparticle-delivered siRNA was associated with increased sensitivity of breast cancer cells to cisplatin. Reduced growth and increased apoptosis of MCF-7 cells were observed in the CXCR4 siRNA group than in the control siRNA group. Taken together, our results present the treatment potential of chitosan nanoparticle-delivered siRNA targeting CXCR4 in breast cancers.