Pancreatic cancer poorly responds to available drugs, and finding novel approaches to target this cancer type is of high significance. Here, based on a common property of pancreatic cancer cells to express somatostatin receptors (SSTR), we designed drug conjugates with novel somatostatin-derived cyclic peptides (SSTp) with broad selectivity towards SSTR types to facilitate drug targeting of the pancreatic cancer cells specifically. Uptake of our newly designed SSTps was facilitated by SSTRs expressed in the pancreatic cancers, including SSTR2, SSTR3, SSTR4 and SSTR5. Three major drugs were conjugated to our best SSTps that served as delivery vehicles, including Camptothecin (CPT), Combretastatin-4A (COMB) and Azatoxin (AZA). All designed drug conjugates demonstrated penetration to pancreatic cancer cell lines, and significant toxicity towards them. Furthermore, the drug conjugates specifically accumulated in tumors in the animal xenograft model, though some accumulation was also seen in kidney. Overall these findings lay the basis for development of novel drug series that could target the fatal pancreatic cancer.

胰腺癌对可用药物的反应较差，因此寻找针对这种癌症类型的新方法具有重要意义。在这里，基于胰腺癌细胞表达生长抑素受体（SSTR）的共同特性，我们设计了具有新型生长抑素衍生的环肽（SSTp）的药物结合物，该结合物对SSTR类型具有广泛的选择性，以促进针对胰腺癌细胞的药物靶向。在胰腺癌中表达的SSTR促进了我们新设计SSTps的吸收，包括SSTR2，SSTR3，SSTR4和SSTR5。三种主要药物与我们作为递送载体的最佳SSTps偶联，包括喜树碱（CPT），Combretastatin-4A（COMB）和Azatoxin（AZA）。所有设计的药物结合物均显示出可渗透至胰腺癌细胞系，并对它们具有明显的毒性。此外，药物缀合物在动物异种移植模型中的肿瘤中特异性蓄积，尽管在肾脏中也观察到一些蓄积。总体而言，这些发现为开发针对致命胰腺癌的新药系列奠定了基础。