Local Sustained Chemotherapy of Pancreatic Cancer Using Endoscopic Ultrasound-Guided Injection of Biodegradable Thermo-Sensitive Hydrogel.
Local Sustained Chemotherapy of Pancreatic Cancer Using Endoscopic Ultrasound-Guided Injection of Biodegradable Thermo-Sensitive Hydrogel.
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DOI：
10.2147/ijn.s417445
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发表时间：
2023
影响因子：
8
通讯作者：
中科院分区：
文献类型：
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内镜超声引导下细针注射（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。可注射的水凝胶可形成药物释放库，这为通过EUS-FNI优化靶向化疗提供了可行的解决方案。以吉西他滨（GEM）和温敏性水凝胶（PLGA-PEG-PLGA，PPP）为载体，制备了一种新型的药物缓释系统。对PPP水凝胶的可注射性、凝胶形成能力、生物相容性和药物缓释性能进行了体内外验证。通过与PANC-1细胞共培养，探讨GEM/PPP水凝胶对PANC-1细胞增殖、侵袭、转移和凋亡的影响。采用精确靶向EUS-FNI技术比较GEM/PPP水凝胶与GEM、乙醇和聚多卡醇对异种移植小鼠的治疗效果。通过H&E、Ki-67和TUNEL染色检查肿瘤切片。GEM/PPP水凝胶表现出优异的注射性、生物相容性和通过由体温触发形成凝胶而持续药物递送长达7天的能力。其表现出最佳的治疗效果，显著降低PANC-1细胞的增殖、侵袭和迁移，同时促进凋亡。在使用EUS-FNI技术精确注射后，GEM/PPP水凝胶导致肿瘤重量减少高达75.96%，存活期延长14.4天，不良反应可忽略不计。病理学检查显示无全身毒性，细胞凋亡明显，增殖极轻微。GEM/PPP水凝胶与EUS-FNI技术的结合，为胰腺癌精准化疗提供了最佳途径，为基础研究的临床转化搭建了桥梁，为微创治疗模式的创新带来了巨大希望。本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。
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. 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. 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. 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.
DOI：
10.1016/j.jconrel.2022.01.023
发表时间：
2022-03
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Pandit S;Palvai S;Massaro NP;Pierce JG;Brudno Y
通讯作者：
Brudno Y