Abstract: OBJECTIVE To prepare self-loaded drug nanoparticles (HA-ss-Bai NPs) with reduction responsiveness and tumor-targeting properties,and to investigate their feasibility as a drug carrier to deliver curcumin (Cur).METHODS The polymer hyaluronic acid (HA)-baicalin (Bai) connected by disulfide bonds was synthesized,and its structure was confirmed by hydrogen nuclear magnetic resonance spectroscopy (¹H-NMR) and infrared spectroscopy (IR).The self-assembled nanoparticles were prepared by the ultrasound method,their particle size and Zeta potential were characterized,and their critical aggregation concentration (CAC) was determined by the pyrene fluorescence probe method;the encapsulation efficiency and drug loading amount of nanoparticles loaded with Cur were determined.The anti-tumor activity in vitro of drug-loaded nanoparticles was assessed by MTT assay.RESULTS HA-ss-Bai NPs were prepared,the minimum particle size was (124.3±6.5) nm,CAC value was (0.023 8±0.003 5) mg·mL^–1.The particle size of Cur/HA-ss-Bai NPs was (172.5±3.2) nm,drug loading was (17.08±0.25)%,encapsulation efficiency was (51.23±3.97)%.The in vitro release showed that the drug could be released quickly under reducing conditions.The MTT experiment indicated that Cur/HA-ss-Bai NPs had a significant inhibitory effect on the growth of HepG2 liver cancer cells.CONCLUSION The Cur/HA-ss-Bai NPs have uniform particle size,with high drug loading,good reduction responsiveness and anti-cancer activity.The anti-tumor effect of Bai and Cur in vitro is improved.