Abstract: Objective To design and synthesize a novel paclitaxel loaded nanoparticle with reactive oxygen species (ROS) response, and characterize its structure, and investigate its stability, in vitro drug responsive release, cellular uptake and in vitro antitumor activity. Methods The PEG- 2S- PTX monomer was synthesized by coupling the hydrophilic polyethylene glycol (PEG) with hydrophobic paclitaxel (PTX) via a thioether chain (2S), and the prodrug nanoparticles (PEG- 2S-PTX NPs) were prepared by self-assembly. Meanwhile, using succinic anhydride (SA) as the linking group to synthesize the PEG-SA-PTX monomer and prepare the other prodrug nanoparticles (PEG-SA-PTX NPs) as control. The structures of PEG-2S-PTX and PEG-SA-PTX monomer were confirmed by 1H-NMR. The diameter and stability of the nanoparticles were detected by dynamic light scattering (DLS). The PTX release kinetics under oxidizing condition was detected by high performance liquid chromatography (HPLC) method. And the cellular uptake efficiency of nanoparticles by MCF-7 cells was observed by fluorescence microscope. The in vitro antitumor effects of nanoparticles were compared by MTT assay. Results PEG-2S-PTX and PEG-SA-PTX could both be self-assemble into nanoparticles with the diameter of (92.15±12.42) nm and (113.20±12.16) nm. PEG-2S-PTX NPs could rapidly release PTX under oxidative condition while PEG-SA-PTX NPs only showed weak responsiveness. PEG-2S-PTX NPs could be more rapidly taken up by MCF-7 cells compared with PEG-SA-PTX NPs. They both showed concentration dependent anti-tumor effects, but the cytotoxicity of PEG-2S-PTX NPs was stronger than that of PEG-SA-PTX NPs in the concentrations of 0.05, 0.1, 5, 10, 50 and 100 mg/L (P＜0.05). Conclusion As paclitaxel prodrug nanoparticles with ROS responsive ability, PEG-2S-PTX NPs can rapidly release PTX in response to ROS in tumor cells, and exhibit great anti-tumor activity in vitro.

Key words: reactive oxygen species, nanoparticles, ROS-responsive, paclitaxel prodrug, self-assembly