【摘要】：Although it is reported that the targeting ability of hyaluronic acid(HA)-based nanoparticles(NPs) is molecular weight(MW) dependent,the influence of HA MW on targeting efficiency of HA-functionalized NPs and the underlying mechanism remain elusive. In this study,we constituted three HA-functionalized Dox-loaded NPs(Dox/HCVs) different HA MWs(7,63,and 102 k Da) and attempted to illustrate the effects of HA MW on the targeting efficiency.The three Dox/HCVs had similar physiochemical and pharmaceutical characteristics,but showed different affinity to CD44 receptor. Furthermore,Dox/HCV-63 exerted the best targeting effect and the highest cytotoxicity compared with Dox/HCV-7 and Dox/HCV-102. It was interesting to found that both the HA-CD44 binding affinity and induced CD44 clustering by HA-based NPs were HA MW-dependent,the two of which determine the apparent targeting efficacy of Dox/HCV NPs in the conflicting directions. Those results laid a good foundation for rationally designing HA-based NPs in cancer therapy.