Silver nanoparticles functionalized Paclitaxel nanocrystals enhance overall anti-cancer effect on human cancer cells.

For chemotherapeutic drugs, precise tumor-targeting and high anti-cancer efficiency is equally important to enhance chemotherapy and reverse drug resistance. The combination of multi-functional agents to achieve synergy should be a promising strategy. In our study, we have successfully developed novel multi-functionalized drug nanocrystals to realize co-delivery of organic drug Paclitaxel (PTX), inorganic silver nanoparticles (AgNPs) and tumor targeting agent. To be specific, PTX nanocrystals were first prepared as a template, followed by polydopamine (PDA) coating. The PDA layer was utilized as connection bridge to produce and deposit AgNPs in situ, and provide sites for tumor-targeting peptide NR1 (RGDARF) grafting. As a result, these NR1/AgNPs decorated drug nanocrystals exhibited dramatically improved cellular uptake efficiency, in vitro anti-cancer activity and anti-migratory effect against a variety of cancer cells, which was attributable to the synergistic or at least additive effect from AgNPs and PTX, enhanced cellular uptake efficiency through NR1-receptor interaction, pH-responsive drug release and nano-scaled nature. In particular, high anti-cancer activity and low side effect from these NR1/AgNPs decorated PTX nanocrystals were well balanced in terms of good selectivity and biocompatibility. Moreover, these novel drug nanocrystals displayed strong apoptotic-inducing potency, resulting in cell membrane lysis, nuclear damage, mitochondria dysfunction, excessive ROS release and double-stranded DNA breakage. The potential acting mechanism and molecular basis of these novel drug nanocrystals is relevant to regulation of mitochondria-mediated apoptosis with greater Bax to Bcl-2 ratio and activation of pro-apoptotic P53 and Caspase 3.