Design and evaluation of dual CD44 receptor and folate receptor-targeting double-smart pH-response multifunctional nanocarrier

  • Daquan ChenEmail author
  • Xiaoyan Song
  • Kaili Wang
  • Chunjing Guo
  • Yueming Yu
  • Huaying Fan
  • Feng Zhao
Brief Communication


In this article, in order to enhance the bioavailiability and tumor targeting of curcumin (Cur), the oligosaccharides of hyaluronan conjugates, folic acid-oligosaccharides of hyaluronan-acetal-menthone 1,2-glycerol ketal (FA-oHA-Ace-MGK) carried oHA as a ligand to CD44 receptor, double-pH-sensitive Ace-MGK as hydrophobic moieties, and FA as the target of folate receptor. The structure characteristics of this smart response multifunctional dual-targeting nano-sized carrier was measured by fourier-transform infrared (FT-IR) and nuclear magnetic resonance (1H–NMR). Cur, an anticancer drug, was successfully loaded in FA-oHA-Ace-MGK micelles by self-assembly. The measurement results of transmission electron microscopy (TEM) presented that the Cur-loaded micelles were spherical in shape with the average size of 166.3 ± 2.12 nm and zeta potential − 30.07 mV. Much more encapsulated Cur could be released at mildly acidic environments than at pH 7.4, from the Cur-FA-oHA-Ace-MGK micelles. Cytotoxicity assay indicated that non-Cur loaded micelles mostly had no cytotoxicity to MCF-7 cells and A549 cells, and Cur-loaded micelles had significantly lower survival rate than Cur suspension in the same concentration, which proved that the drug-loaded micelles can effectively inhibit tumor cell growth. The targeting of CD44 receptors and folate receptors was proved in vitro cellular uptake assay. These results showed the promising potential of FA-oHA-Ace-MGK as an effective nano-sized carrier for anti-tumor drug delivery.


CD44 receptor and folate receptor dual targeting Double pH-sensitivity Oligosaccharides of hyaluronan (oHA) conjugates Drug delivery Curcumin nanoparticles 


Author contributions

All the authors contributed equally to this work.

Funding information

This work was supported by the National Natural Science Foundation of China (No. 81573614), Young Taishan Scholar Program (No. qnts 20161035), the Graduate Innovation Foundation of Yantai University (No. YDYB1726), and the Technical Project of Yantai City (2015ZH079).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.


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Copyright information

© Springer Science+Business Media B.V., part of Springer Nature 2017

Authors and Affiliations

  1. 1.School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery, System and Biotech Drugs in Universities of ShandongYantai UniversityShandong ShengChina
  2. 2.State Key Laboratory of Long-acting and Targeting Drug Delivery SystemYantaiChina

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