■内镜超声引导细针注射(EUS-FNI)为晚期胰腺癌的局部靶向治疗提供了一种有前途的微创方法。然而,由于化疗剂的快速血浆清除,疗效有限。可注射水凝胶可以形成药物释放库,这为通过EUS-FNI优化靶向化疗提供了可行的解决方案。
■开发了一种药物递送系统,由吉西他滨(GEM)和热敏水凝胶(PLGA-PEG-PLGA,PPP)。可注射性,凝胶形成能力,在体外和体内验证了PPP水凝胶的生物相容性和持续给药性能。GEM/PPP水凝胶对细胞增殖的影响,入侵,转移,通过与PANC-1细胞共培养探索细胞凋亡。比较GEM/PPP水凝胶对异种移植小鼠的治疗效果,使用精确靶向的EUS-FNI技术的乙醇和脊髓灰质炎。通过H&E检查肿瘤切片,Ki-67和TUNEL染色。
■GEM/PPP水凝胶表现出优异的可注射性,生物相容性,以及通过形成由体温触发的凝胶来持续药物递送长达7天的能力。它显示出最好的治疗效果,显著减少扩散,PANC-1细胞的侵袭和迁移同时促进凋亡。使用EUS-FNI技术进行精确注射后,GEM/PPP水凝胶导致肿瘤重量减少高达75.96%,并将生存期延长14.4天,不良反应可忽略不计。病理检查显示无全身毒性,明显的细胞凋亡和最小的增殖。
■GEM/PPP水凝胶和EUS-FNI技术的结合为胰腺癌提供了精确化疗的最佳途径,为基础研究的临床翻译搭建桥梁,并为微创治疗方式的创新带来了巨大的希望。在这项研究中获得的第一手EUS图像数据也可作为未来临床试验的重要参考。
UNASSIGNED: Endoscopic ultrasound-guided fine-needle injection (EUS-FNI) offers a promising minimally invasive approach for locally targeted management of advanced pancreatic cancer. However, the efficacy is limited due to the rapid plasma clearance of chemotherapeutic agents. Injectable hydrogels can form drug release depots, which provide a feasible solution for optimizing targeted chemotherapy through EUS-FNI.
UNASSIGNED: A drug delivery system was developed, consisting of gemcitabine (GEM) and thermo-sensitive hydrogel (PLGA-PEG-PLGA, PPP). The injectability, gel formation ability, biocompatibility and sustained drug delivery properties of PPP hydrogel were verified in vitro and in vivo. The effects of GEM/PPP hydrogel on cell proliferation, invasion, metastasis, and apoptosis were explored through co-culturing with PANC-1 cells. The therapeutic effects of GEM/PPP hydrogel on xenograft mice were compared with those of GEM, ethanol and polidocanol using the precisely targeted EUS-FNI technology. Tumor sections were examined by H&E, Ki-67, and TUNEL staining.
UNASSIGNED: GEM/PPP hydrogel exhibited excellent injectability, biocompatibility, and the capability of sustained drug delivery for up to 7 days by forming a gel triggered by body temperature. It demonstrated the best therapeutic effects, significantly reducing proliferation, invasion and migration of PANC-1 cells while promoting apoptosis. After precise injection using EUS-FNI technology, GEM/PPP hydrogel resulted in a reduction of tumor weight by up to 75.96% and extending the survival period by 14.4 days with negligible adverse effects. Pathological examination revealed no systemic toxicity and significant apoptosis and minimal proliferation as well.
UNASSIGNED: The combination of GEM/PPP hydrogel and EUS-FNI technology provides an optimal approach of precise chemotherapy for pancreatic cancer, builds a bridge for clinical translation of basic research, and brings great hope for innovation of minimally invasive treatment modalities. The first-hand EUS image data obtained in this study also serves as a crucial reference for future clinical trials.