Citation: Bei-bei Lu, Lu-lu Wei, Gui-hua Meng, Jun Hou, Zhi-yong Liu, Xu-hong Guo. Synthesis of Self-assemble pH-responsive Cyclodextrin Block Copolymer for Sustained Anticancer Drug Delivery[J]. Chinese Journal of Polymer Science, ;2017, 35(8): 924-938. doi: 10.1007/s10118-017-1947-0 shu

Synthesis of Self-assemble pH-responsive Cyclodextrin Block Copolymer for Sustained Anticancer Drug Delivery

Bei-bei Lu ^a ,
Lu-lu Wei ^a ,
Gui-hua Meng ^a ,
Jun Hou ^b ,
Zhi-yong Liu ^a,, ,
Xu-hong Guo ^a,c

a.
School of Chemistry & Chemical Engineering, Shihezi University/Key Laboratory of Materials-Oriented Chemical Engineering of Xinjiang Uygur Autonomous Region/Engineering Research Center of Materials-Oriented Chemical Engineering of Xinjiang Bingtuan, Shihezi 832003, China
b.
Department of Immunology, Shihezi University School of Medicine/Department of Pathology and Key Laboratories for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi 832003, China
c.
State Key Laboratory of Chemical Engineering, East China University of Science and Technology, Shanghai 200237, China

Corresponding author: Zhi-yong Liu, lzyongclin@sina.com
Received Date: 14 January 2017
Revised Date: 28 February 2017
Accepted Date: 1 March 2017

Fund Project: the National Natural Science Foundation of China 21367022Bingtuan Innovation Team in Key Areas 2015BD003

Well-defined pH-responsive poly(ε-caprolactone)-graft-β-cyclodextrin-graft-poly(2-(dimethylamino)ethyl-methacrylate)-co-poly(ethylene glycol) methacrylate amphiphilic copolymers (PCL-g-β-CD-g-P(DMAEMA-co-PEGMA)) were synthesized using a combination of atom transfer radical polymerization (ATRP), ring opening polymerization (ROP) and "click" chemistry. Successful synthesis of polymers was confirmed by Fourier transform infrared spectroscopy (FTIR), proton nuclear magnetic resonance (¹H-NMR), and gel permeation chromatography (GPC). Then, the polymers could self-assemble into micelles in aqueous solution, which was demonstrated by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The pH-responsive self-assembly behavior of these copolymers in water was investigated at different pH values of 7.4 and 5.0 for controlled doxorubicin (DOX) release, and these results revealed that the release rate of DOX could be effectively controlled by altering the pH, and the release of drug loading efficiency (DLE) was up to 88% (W/W). CCK-8 assays showed that the copolymers had low toxicity and possessed good biodegradability and biocompatibility, whereas the DOX-loaded micelles remained with high cytotoxicity for HeLa cells. Moreover, confocal laser scanning microscopy (CLSM) images revealed that polymeric micelles could actively target the tumor site and the efficient intracellular DOX release from polymeric micelles toward the tumor cells further confirmed the anti-tumor effect. The DOX-loaded micelles could easily enter the cells and produce the desired pharmacological action and minimize the side effect of free DOX. These results successfully indicated that pH-responsive polymeric micelles could be potential hydrophobic drug delivery carriers for cancer targeting therapy with sustained release.
- pH-responsive,
- β-Cyclodextrin,
- Self-assembly,
- DOX,
- Controlled release,
- Click chemistry
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