Design, synthesis, and in vitro antitumor activity of a transferrin receptor-targeted peptide-doxorubicin conjugate

  • Chem Biol Drug Des. 2020 Jan;95(1):58-65. doi: 10.1111/cbdd.13613.
Songtao Li  1 ,  Hongling Zhao  1 ,  Yanfang Fan  2 ,  Guiqin Zhao  1 ,  Ruxing Wang  1 ,  Fuyu Wen  1 ,  Jianping Wang  3 ,  Xiaohui Wang  2 ,  Yu Wang  4 ,  Yang Gao  1
Affiliations
  • 1. Hebei Province Key Laboratory of Research and Development of Traditional Chinese Medicine, Institute of Chinese Mateia Medica, Chengde Medical University, Chengde, China.
  • 2. Institute of Basic Medicine, Chengde Medical University, Chengde, China.
  • 3. Department of Immunology, Chengde Medical University, Chengde, China.
  • 4. Department of Traumatic Orthopaedics, Affiliated Hospital of Chengde Medical University, Chengde, China.
PMID: 31452330 DOI: 10.1111/cbdd.13613
Abstract

In this study, a peptide-drug conjugate was designed and synthesized by connecting a Transferrin Receptor (TfR)-targeted binding peptide analog BP9a (CAHLHNRS) with doxorubicin (DOX) through N-succinimidyl-3-maleimidopropionate (SMP) as the cross-linker. Confocal laser scanning microscopy results indicated that free DOX mainly accumulated in the nuclei of both TfR overexpressed HepG2 hepatoma cells and L-O2 normal liver cells expressing low level of TfR; most of the BP9a-DOX conjugate displayed cytoplasmic location, and its cellular uptake by HepG2 cells was obviously reduced by TfR blockage test. Nevertheless, the cellular uptake of this conjugate by L-O2 cells was much less than that of free DOX. Meanwhile, the BP9a-DOX conjugate exhibited lower in vitro antiproliferative activity against HepG2 cells than free DOX, but its cytotoxic effect on L-O2 cells was decreased compared with that of free DOX. These results suggest that BP9a could be applied as a potential TfR-targeted peptide vector for selective Drug Delivery.

Keywords
doxorubicin; peptide-drug conjugate; synthesis; targeted antitumor activity; transferrin receptor.
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