生长抑素受体介导的精准递送：通过在胰腺癌治疗中偶联奥曲肽克服雷公藤内酯醇的局限性
SSTR-Mediated Precision Delivery: Overcoming Triptolide's Limitations through Octreotide Conjugation in Pancreatic Cancer Treatment.
作者信息
Su Dandan, Bao Qiaohong, Wang Xinyu, Qian Jiecheng, Zhang Muzihe, Chen Jianming, Wu Xin
机构信息
Fujian University of Traditional Chinese Medicine, No. 1 Qiuyang Road, Fuzhou 350122, China.
Shanghai Wei Er Lab, Shanghai 201707, China.
出版信息
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。
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