Depau Lorenzo, Brunetti Jlenia, Falciani Chiara, Scali Silvia, Riolo Giulia, Mandarini Elisabetta, Pini Alessandro, Bracci Luisa
Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy.
Oncotarget. 2017 Jul 6;8(44):76141-76152. doi: 10.18632/oncotarget.19056. eCollection 2017 Sep 29.
Cancer-selective tetra-branched peptides, named NT4, can be coupled to different functional units for cancer cell imaging or therapy. NT4 peptides specifically bind to lipoprotein receptor-related proteins (LRP) receptors and to heparan sulfate chains on membrane proteoglycans and can be efficiently internalized by cancer cells expressing these membrane targets. Since binding and internalization of NT4 peptides is mediated by specific NT4 receptors on cancer cell membranes and this may allow drug resistance produced by drug membrane transporters to be by-passed, we tested the ability of drug-armed NT4 to by-pass drug resistance in cancer cell lines. We found that MTX-conjugated NT4 allows drug resistance to be by-passed in MTX-resistant human breast cancer cells lacking expression of folate reduced carrier. NT4 peptides appear to be extremely promising cancer-selective targeting agents that can be exploited as theranostics in personalized oncological applications.
名为NT4的癌症选择性四分支肽可与不同功能单元偶联，用于癌细胞成像或治疗。NT4肽特异性结合脂蛋白受体相关蛋白（LRP）受体以及膜蛋白聚糖上的硫酸乙酰肝素链，并可被表达这些膜靶点的癌细胞有效内化。由于NT4肽的结合和内化是由癌细胞膜上的特定NT4受体介导的，这可能使药物膜转运蛋白产生的耐药性得以绕过，因此我们测试了载药NT4绕过癌细胞系中耐药性的能力。我们发现，与甲氨蝶呤（MTX）偶联的NT4能够在缺乏叶酸还原载体表达的MTX耐药人乳腺癌细胞中绕过耐药性。NT4肽似乎是极具前景的癌症选择性靶向剂，可在个性化肿瘤应用中用作治疗诊断剂。
