Su Dandan, Bao Qiaohong, Wang Xinyu, Qian Jiecheng, Zhang Muzihe, Chen Jianming, Wu Xin
Fujian University of Traditional Chinese Medicine, No. 1 Qiuyang Road, Fuzhou 350122, China.
Shanghai Wei Er Lab, Shanghai 201707, China.
ACS Med Chem Lett. 2025 May 13;16(6):1048-1057. doi: 10.1021/acsmedchemlett.5c00097. eCollection 2025 Jun 12.
Pancreatic cancer, a highly aggressive malignancy, primarily relies on chemotherapy, with existing drugs showing limited efficacy and selectivity. Triptolide (TPL), a broad-spectrum anticancer agent, exhibits potent antitumor activity but suffers from high toxicity, poor selectivity, and low water solubility. To address these limitations, we constructed the targeted prodrug TPL-OCT by conjugating TPL with octreotide (OCT), a somatostatin receptor (SSTR)-specific ligand highly expressed in pancreatic cancer cells, using succinic anhydride as a linker. This novel strategy simultaneously enhanced TPL's physicochemical properties (particularly aqueous solubility) through chemical modification and achieved tumor-targeted delivery via SSTR-mediated specificity. The optimized prodrug demonstrates improved therapeutic safety and efficacy, offering a promising approach for pancreatic cancer treatment.
胰腺癌是一种极具侵袭性的恶性肿瘤，主要依赖化疗，现有药物的疗效和选择性有限。雷公藤甲素（TPL）是一种广谱抗癌剂，具有强大的抗肿瘤活性，但存在高毒性、低选择性和低水溶性的问题。为了解决这些局限性，我们以琥珀酸酐为连接体，将TPL与在胰腺癌细胞中高表达的生长抑素受体（SSTR）特异性配体奥曲肽（OCT）偶联，构建了靶向前药TPL-OCT。这种新策略通过化学修饰同时增强了TPL的物理化学性质（特别是水溶性），并通过SSTR介导的特异性实现了肿瘤靶向递送。优化后的前药显示出更高的治疗安全性和疗效，为胰腺癌治疗提供了一种有前景的方法。
