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Design, synthesis, and in vitro antitumor activity of a transferrin receptor-targeted peptide-doxorubicin conjugate.
Chemical Biology & Drug Design ( IF 3.2 ) Pub Date : 2019-10-03 , 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
Chemical Biology & Drug Design ( IF 3.2 ) Pub Date : 2019-10-03 , 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
Affiliation
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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.
中文翻译：
设计，合成和体外抗肿瘤活性的转铁蛋白受体靶向肽-阿霉素结合物。
在这项研究中，通过将靶向转铁蛋白受体（TfR）的结合肽类似物BP9a（CAHLHNRS）与阿霉素（DOX）通过N-琥珀酰亚胺基-3-马来酰亚胺基丙酸酯（SMP）连接，设计并合成了一种肽-药物偶联物。链接器。共聚焦激光扫描显微镜结果表明，游离的DOX主要积累在TfR过表达的HepG2肝癌细胞和表达低水平TfR的L-O2正常肝细胞的细胞核中。大部分的BP9a-DOX结合物都显示出胞质位置，并且通过TfR阻断试验明显降低了HepG2细胞对细胞的摄取。然而，L-O2细胞对这种结合物的细胞摄取比游离DOX少得多。同时，BP9a-DOX缀合物对HepG2细胞的体外抗增殖活性低于游离的DOX，但是它对L-O2细胞的细胞毒性作用比游离DOX要低。这些结果表明，BP9a可用作潜在的TfR靶向肽载体，用于选择性药物递送。
更新日期：2019-10-10
中文翻译：
设计，合成和体外抗肿瘤活性的转铁蛋白受体靶向肽-阿霉素结合物。
在这项研究中，通过将靶向转铁蛋白受体（TfR）的结合肽类似物BP9a（CAHLHNRS）与阿霉素（DOX）通过N-琥珀酰亚胺基-3-马来酰亚胺基丙酸酯（SMP）连接，设计并合成了一种肽-药物偶联物。链接器。共聚焦激光扫描显微镜结果表明，游离的DOX主要积累在TfR过表达的HepG2肝癌细胞和表达低水平TfR的L-O2正常肝细胞的细胞核中。大部分的BP9a-DOX结合物都显示出胞质位置，并且通过TfR阻断试验明显降低了HepG2细胞对细胞的摄取。然而，L-O2细胞对这种结合物的细胞摄取比游离DOX少得多。同时，BP9a-DOX缀合物对HepG2细胞的体外抗增殖活性低于游离的DOX，但是它对L-O2细胞的细胞毒性作用比游离DOX要低。这些结果表明，BP9a可用作潜在的TfR靶向肽载体，用于选择性药物递送。
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