Combination treatment based on gene and
chemotherapy is a promising strategy for effective
cancer treatment due to the limited therapeutic efficacy of anticancer drugs. Dual functional polymeric
micelles (PMs) have been emerged as potent nanocarriers for combinational
cancer therapy. In the present study, the potential of tri-layer PMs loaded with anti-nuclear factor-κB (NF-κB)
siRNA and 4-(N)-stearoyl
gemcitabine (GemC18) has been investigated for
cancer treatment. PMs with different core hydrophobicity were prepared by using poly(ε-
caprolactone),
polyethyleneimine and
polyethylene glycol (PCL-PEI-PEG) copolymers and evaluated. The results revealed that GemC18-loaded PMs were significantly more cytotoxic than free drug on breast and
pancreatic cancer cells. However, the cytotoxicity of drug loaded
micelles was decreased by increasing the micellar core hydrophobicity because of decreasing drug release rate. Moreover,
siRNA loaded PMs could considerably inhibit NF-κB expression. PMs loaded with both GemC18 and
siRNA exhibited higher capability to induce apoptosis and inhibit migration of both cells. PMs with the most hydrophobic core indicated higher
tumor accumulation efficiency via in-vivo imaging study. In conclusion, the prepared PMs hold a promise as an attractive dual functional delivery system for an effective
cancer therapy.