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
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  • Supported by:
    National Natural Science Foundation of China (Grant No. 81673366).


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

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