Liu Jiefeng, Gong Yujing, Zeng Xinyu, He Miao, He Bin, Gao Wenbin, Gao Yong
Department of General Surgery, Changsha Hospital Affiliated to Hunan Normal University, The Fourth Hospital of Changsha, No. 200 Jinxing Road, Wangcheng District, Changsha, 410219, Hunan, China.
BMC Cancer. 2025 May 26;25(1):944. doi: 10.1186/s12885-025-14356-w.
Pancreatic cancer is a malignancy with poor prognosis and high mortality. This study investigated the use of chitosan nanoparticles (CS-NPs) to encapsulate AMTB, a TRPM8 inhibitor, as a novel strategy to enhance therapeutic efficacy in pancreatic cancer. TRPM8 was overexpressed in pancreatic cancer tissues and associated with poor patient prognosis. AMTB inhibited pancreatic cancer cell proliferation, migration, and invasion by suppressing the EMT process and MMP2/9 expression. CS-NPs@AMTB were successfully synthesized, exhibiting excellent drug release profiles and stronger anti-tumor effects than free AMTB. Both AMTB and CS-NPs@AMTB demonstrated favorable biological safety. This is the first study to apply chitosan nanoparticles for AMTB delivery in pancreatic cancer, significantly enhancing its anti-tumor and anti-metastatic effects (ahout 70% reduction in tumor size). These findings suggest that CS-NPs@AMTB might overcome current therapeutic limitations by improving drug efficacy and targeting metastasis in pancreatic cancer. With further validation through preclinical and clinical studies, this nanoparticle-based delivery strategy holds promise for integration into future therapeutic regimens and personalized treatment approaches.
胰腺癌是一种预后差、死亡率高的恶性肿瘤。本研究探讨了使用壳聚糖纳米颗粒（CS-NPs）包裹TRPM8抑制剂AMTB，作为提高胰腺癌治疗效果的新策略。TRPM8在胰腺癌组织中过表达，且与患者预后不良相关。AMTB通过抑制EMT过程和MMP2/9表达来抑制胰腺癌细胞的增殖、迁移和侵袭。成功合成了CS-NPs@AMTB，其表现出优异的药物释放曲线，且抗肿瘤作用比游离AMTB更强。AMTB和CS-NPs@AMTB均显示出良好的生物安全性。这是第一项将壳聚糖纳米颗粒用于在胰腺癌中递送AMTB的研究，显著增强了其抗肿瘤和抗转移作用（肿瘤大小减少约70%）。这些发现表明，CS-NPs@AMTB可能通过提高药物疗效和靶向胰腺癌转移来克服当前的治疗局限性。通过临床前和临床研究进一步验证后，这种基于纳米颗粒的递送策略有望整合到未来的治疗方案和个性化治疗方法中。
