Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Republic of Korea.
Department of Minimal-Invasive Intervention, The Affiliated Cancer Hospital of Zhengzhou University, 127 Dongming Road, Zhengzhou 450003, Henan Province, China.
ACS Biomater Sci Eng. 2021 Dec 13;7(12):5890-5898. doi: 10.1021/acsbiomaterials.1c01166. Epub 2021 Nov 24.
The self-expanding metal stent (SEMS) is a versatile, palliative treatment method for unresectable, malignant, non-vascular strictures. Colorectal cancer (CRC) is one of the candidates for the application of the SEMS, in combination with the photothermal ablation (PTA) technique that enhances its therapeutic efficacy. The objective of this study was to investigate the efficacy of stent-mediated PTA therapy in an endoscopy-guided, orthotopic rectal cancer model. A total of 30 of 40 mice with the tumor size of grade 4 were included and were divided into three groups of 10 mice each. Group A underwent a gold nanoparticle (AuNP)-coated SEMS but no near-infrared (NIR) irradiation, group B received an uncoated control SEMS with NIR irradiation, and group C received a AuNP-coated SEMS and NIR irradiation together. Colonoscopy and imaging, immunohistochemical analysis, and quantitative reverse-transcription polymerase chain reaction of major tumor markers were performed. Stent placement and PTA were technically successful using colonoscopy. The tumor grade reduction after PTA is significant in group C, compared with groups A or B ( < 0.001). Molecular analysis validated this observation with a significantly reduced Mapk1 proliferation marker or increased Jnk expression. Histological analysis confirmed the localized PTA therapy using AuNP-coated SEMS profoundly ablated tumor outgrowth through the stent. Our results indicate that this novel strategy of localized PTA therapy could be a promising option for palliative treatment of CRC and to support prolonged stent patency with a decreased tumor volume.
自膨式金属支架（SEMS）是一种多功能的姑息性治疗方法，适用于无法切除的恶性非血管狭窄。结直肠癌（CRC）是 SEMS 应用的候选者之一，结合光热消融（PTA）技术可增强其治疗效果。本研究旨在探讨支架介导的 PTA 治疗在经内镜引导的原位直肠癌模型中的疗效。共纳入 40 只肿瘤大小为 4 级的小鼠，其中 30 只被分为 3 组，每组 10 只。A 组接受载金纳米颗粒（AuNP）的 SEMS 但不接受近红外（NIR）照射，B 组接受未涂层的对照 SEMS 加 NIR 照射，C 组接受载 AuNP 的 SEMS 加 NIR 照射。进行结肠镜检查和成像、免疫组织化学分析以及主要肿瘤标志物的定量逆转录聚合酶链反应。通过结肠镜检查成功进行了支架放置和 PTA。与 A 组或 B 组相比，C 组 PTA 后肿瘤分级降低具有统计学意义（<0.001）。分子分析证实了这一观察结果，即增殖标志物 Mapk1 减少或 Jnk 表达增加。组织学分析证实了使用载 AuNP 的 SEMS 进行局部 PTA 治疗可通过支架深度消融肿瘤生长。我们的结果表明，这种局部 PTA 治疗的新策略可能是 CRC 姑息治疗的有前途的选择，并可减少肿瘤体积以支持延长支架通畅性。
