Co-Delivery of Gemcitabine Prodrug Along With Anti Nf-Κb Sirna by Tri-Layer Micelles Can Increase Cytotoxicity, Uptake and Accumulation of the System in the Cancers Publisher Pubmed



Norouzi P¹ ; Amini M² ; Dinarvand R^{1, 3} ; Arefian E⁴ ; Seyedjafari E⁵ ; Atyabi F^{1, 3} Show Affiliations
Source: Materials Science and Engineering C Published:2020

Abstract

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. © 2020 Elsevier B.V.