http://www.jcps.ac.cn

Journal of Chinese Pharmaceutical Sciences ›› 2020, Vol. 29 ›› Issue (9): 626-636.DOI: 10.5246/jcps.2020.09.058

• Original articles • Previous Articles     Next Articles

Enhanced tumor-targeted delivery of anticancer drugs by folic acid-conjugated pH-sensitive polymeric micelles

Chuhang Zhou, Xinping Hu, Qi Liu, Leqi Wang, Yuanhang Zhou, Yao Jin, Yan Liu*   

  1. Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China
  • Received:2020-06-12 Revised:2020-07-25 Online:2020-09-30 Published:2020-09-01
  • Contact: Tel.: +86-10-82801508, E-mail: yanliu@bjmu.edu.cn
  • Supported by:
    National Natural Science Foundation of China (Grant No. 81673366).

Abstract:

In order to enhance the targeted delivery of anticancer drugs by polymeric micelles, folic acid (FA), the ligand of folate receptor (FR) over-expressed in the most cancer cells, modified pH-sensitive polymeric micelles were designed and fabricated to encapsulate doxorubicin (DOX) by combination of pH-sensitive amphiphilic polymer poly(2-ethyl-2-oxazoline)-poly(D,L-lactide) with FA-conjugated poly(2-ethyl-2-oxazoline)-poly(D,L-lactide). The prepared micelles were characterized to have about 36 nm in diameter with narrow distribution, well-defined spherical shape observed under TEM and pH-responsive drug release behavior. Moreover, the tumor targeting ability of the FA-modified pH-sensitive polymeric micelles was demonstrated by the cellular uptake, in vitro cytotoxicity to FR-positive KB cells and in vivo real time near-infrared fluorescence imaging in KB tumor-bearing nude mice. The efficient drug delivery by the micelles was ascribed to the synergistic effects of FR-mediated targeting and pH-triggered drug release. In conclusion, the designed FR-targeted pH-sensitive polymeric micelles might be of great potential in tumor targeted delivery of water-insoluble anticancer drugs. 

Key words: pH-sensitive polymeric micelles, Folate receptor-targeted, Tumor-targeted delivery, Cell uptake, Doxorubicin

CLC Number: 

Supporting: