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

Drug Delivery

Mingming Gao¹  Feng Zhao²  Jingfang Sun²  Zongliang Liu²  Daquan Chen²  Shengnan Lian²  Wanhui Liu³  Fenghua Fu³  Yongtao Jiang³  Kaoxiang Sun³ 

[1] College of Pharmacy, University of Georgia, Athens, GA, US;School of Pharmacy, Yantai University, Yantai, People’s Republic of China;School of Pharmacy, Yantai University, Yantai, People’s Republic of China;State Key Laboratory of Long-acting and Targeting Drug Delivery System, Yantai, People’s Republic of China, an;

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

DOI  :  10.3109/10717544.2014.917130

来源: publisher

【 摘 要 】

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.

【 授权许可】

Unknown