Silica nanoparticle-based dual-responsive nanoprodrug system for liver cancer therapy

Abstract

A thiol-terminated polyethyleneglycol (PEG)-paclitaxel (PTX) conjugate was synthesized and utilized to construct a novel drug delivery system with thiol-functionalized silica nanoparticles (SLNs) to improve the overall performance of PTX in liver cancer therapy. Drug loading was performed by coating the PTX conjugate on the surface of SLNs. The PTX-PEG/SLNs showed a binary responsive drug release behavior to esterase as well as high concentrations of glutathione. The synergic effects of these cancer cell-specific factors on the release characteristics of PTX-PEG/SLNs resulted in a significantly (P<0.01) elevated anti-cancer efficiency. This included prolonged circulation and passive tumor-targeting properties in vivo due to surface modification of PEG and targeted release of PTX inside tumor cells, which resulted in increased anti-cancer efficiency. Improving the in vitro properties of PTX-PEG/SLNs not only significantly (P<0.01) enhanced its therapeutic efficacy in a murine liver cancer model, but rendered these drug-conjugated SLNs a promising nanoprodrug system for potential use as clinical cancer therapeutics.