Abstract: OBJECTIVE To prepare surface modified calcium carbonate nanoparticles with glycyrrhetinic acid/sodium alginate and to evaluate its properties. METHODS The hollow spherical calcium carbonate nanoparticles(CaCO₃ Nps) were prepared using soluble starch as organic templates. Glycyrrhetinic acid/sodium alginate copolymer(GA-ALG) was synthesized in heterogeneous system. GA-ALG-CaCO₃ Nps with shell-core structure were synthesized by using GA-ALG as shell and hollow CaCO₃ nanoparticles as core. The particle size distribution and Zeta potential of nanoparticles were measured by Malvern particle size analyzer, and the morphology of nanoparticles was characterized by SEM and TEM. The drug loading, entrapment efficiency and in vitro release characteristics of nanoparticles loaded with doxorubicin hydrochloride(DOX) was evaluated by fluorescence spectrophotometer. RESULTS The average size of GA-ALG-CaCO₃ Nps was (425.4±31.1)nm, PDI was 0.289, Zeta potential was (-17.0±0.3)mV, drug loading was (13.06±0.51)%, encapsulation efficiency was (78.35±3.08)%. In vitro release results showed that nanoparticles had a certain sustained release effect. The results of studies on liver-targeting showed that the targeting efficiency of DOX/GA-ALG-CaCO₃ Nps was 68.2%, which was much higher than the DOX control group's 24.2%. CONCLUSION As a new drug carrier, GA-ALG-CaCO₃ Nps has good pH responsiveness, can significantly increase drug loading, and has obvious sustained release effect and a better liver-targeting capacity.