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Design, synthesis, and in vitro antitumor activity of a transferrin receptor‐targeted peptide–doxorubicin conjugate
Author(s) -
Li Songtao,
Zhao Hongling,
Fan Yanfang,
Zhao Guiqin,
Wang Ruxing,
Wen Fuyu,
Wang Jianping,
Wang Xiaohui,
Wang Yu,
Gao Yang
Publication year - 2020
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.13613
Subject(s) - conjugate , transferrin receptor , doxorubicin , in vitro , peptide , chemistry , linker , transferrin , endocytosis , cytotoxic t cell , cytotoxicity , biochemistry , confocal microscopy , drug delivery , microbiology and biotechnology , pharmacology , receptor , biology , chemotherapy , mathematical analysis , mathematics , genetics , organic chemistry , computer science , operating system
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.