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Drug Deliv. 2016;23(3):808-13. doi: 10.3109/10717544.2014.917130. Epub 2014 Jun 3.

Design of novel multifunctional targeting nano-carrier drug delivery system based on CD44 receptor and tumor microenvironment pH condition.

Chen D1, Lian S1, Sun J1, Liu Z1, Zhao F1, Jiang Y1,2, Gao M3, Sun K1,2, Liu W1,2, Fu F1,2.

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a School of Pharmacy, Yantai University , Yantai , People's Republic of China .
b State Key Laboratory of Long-acting and Targeting Drug Delivery System , Yantai , People's Republic of China , and.
c College of Pharmacy, University of Georgia , Athens , GA , USA.


In this study, to develop a multifunctional targeting nano-carrier drug delivery system for cancer therapy, the novel pH-sensitive ketal based oligosaccharides of hyaluronan (oHA) conjugates were synthesized by chemical conjugation of hydrophobic menthone 1,2-glycerol ketal (MGK) to the backbone of oHA with the histidine as the linker of proton sponge effect. The multifunctional oHA conjugates, oHA-histidine-MGK (oHM) carried the pH-sensitive MGK as hydrophobic moieties and oHA as the target of CD44 receptor. The oHM could self-assemble to nano-sized spherical shape with the average diameters of 128.6 nm at pH 7.4 PBS conditions. The oHM nanoparticles (oHMN) could release encapsulated curcumin (Cur) with 82.6% at pH 5.0 compared with 49.3% at pH 7.4. The results of cytotoxicity assay indicated that encapsulated Cur in oHMN (Cur-oHMN) were stable and have less toxicity compared to Cur suspension. The anti-tumor efficacy in vivo suggested that Cur-oHMN suppressed tumor growth most efficiently. These results present the promising potential of oHMN as a stable and effective nano-sized pH-sensitive drug delivery system for cancer treatment.


2-glycerol ketal (oHM); Drug delivery; nanoparticles; oHA-histidine– menthone 1; oligosaccharides of hyaluronan (oHA); pH-sensitive

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