In this article, we prepared a multifunctional oligosaccharides of hyaluronan (oHA) conjugates, oHA-histidine-menthone 1,2-glycerol ketal (oHM).The oHM conjugates possess pH-sensitive menthone 1,2-glycerol ketal (MGK) as hydrophobic moieties and oHA as the target of CD44 receptor.The polymeric mPEG-Chitosan-Ketal (PCK) carrying pH-sensitive ketal group as hydrophobic moieties and PEG group as hydrophilic moieties were synthesized.The two pH-sensitive ketal derivatives were employed to fabricate nanoparticles for antitumor drug delivery.The oHM-PCK nanoparticles (oHPN) can spontaneously self-assemble into mixed micellar structure with nano-sized spherical shape of 100-200 nm at pH 7.4 PBS conditions.The oHPN could release encapsulated curcumin with 92.6% at pH 5.0 compared with 55.3% at pH 7.4.The results of cytotoxicity assay indicated that encapsulated curcumin in oHPN (Cur-oHPN) have less toxicity compared to curcumin suspensior.The anti-tumor efficacy in vivo suggested that Cur-oHPN suppressed tumor growth most efficiently.These results present the promising potential of oHPN as a new and effective nano-sized pH-sensitive drug delivery system.