SSTR-Mediated Precision Delivery: Overcoming Triptolide's Limitations through Octreotide Conjugation in Pancreatic...

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.