Abstract
Folate (FA) modified amphiphilic linoleic acid (LA) and poly (β-malic acid) (PMLA) double grafted chitosan (LMC) nanoparticles (NPs) with optimum grafting degrees of hydrophobic LA and hydrophilic PMLA were developed for the co-delivery of paclitaxel (PTX) and survivin shRNA-expressing plasmid (iSur-pDNA). The resultant NPs exhibited particle size of 161 nm and zeta potential of 43 mV. FA modification and the increasing grafting degrees of LA and PMLA were correlated with the suppressed protein adsorption, the inhibited release of PTX, and the accelerated dissociation of pDNA. PTX loading, cellular uptake, nuclear accumulation of pDNA, in vitro gene silencing efficiency, and cell growth inhibition were promoted by FA modification and higher grafting degree of LA, but impeded by increasing grafting degree of PMLA. In tumor-bearing mice, co-delivery of PTX and iSur-pDNA exhibited enhanced antitumor efficacy and prolonged survival period as compared with single delivery of PTX or iSur-pDNA. These results indicated that amphiphilic LMC NPs could serve as a promising platform for the co-delivery of antitumor drugs and genes, and highlighted the importance of adjusting the hydrophobic and hydrophilic grafting degrees.