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用于恶性食管癌微创局部治疗的带有集成光敏剂的硅胶覆盖膜的光响应性自膨胀导管。

Photo-responsive self-expanding catheter with photosensitizer-integrated silicone-covered membrane for minimally invasive local therapy in malignant esophageal cancer.

作者信息

Ryu Dae Sung, Lee Hyeonseung, Eo Seung Jin, Kim Ji Won, Kim Yuri, Kang Seokin, Noh Jin Hee, Lee Sanghee, Park Jung-Hoon, Na Kun, Kim Do Hoon

机构信息

Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea; Biomedical Engineering Research Center, Asan Institute for Life Sciences, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea.

Department of Biotechnology, Department of Biomedical-Chemical Engineering, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do, 14662, Republic of Korea.

出版信息

Biomaterials. 2025 Sep;320:123265. doi: 10.1016/j.biomaterials.2025.123265. Epub 2025 Mar 19.

DOI:
10.1016/j.biomaterials.2025.123265
PMID:40121828
Abstract

Photodynamic therapy (PDT) using photosensitizer (PS)-integrated covered self-expandable metallic stents (SEMS) is proposed a new therapeutic approach for the treatment of palliative malignancies; however, the currently hydrophobic PS reduces the photoreactive effect, which leads to aggregation with low water solubility. In here, an aluminum (III)-phthalocyanine chloride tetrasulfonic acid (Al-PcS4)-integrated silicone-covered self-expanding catheter was successfully fabricated to perform localized PDT. The ratio of MeOH and Al-PcS4 concentrations was optimized to achieve PS coating uniformity. The photodynamic activity of the Al-PcS4-integrated silicone membrane was evaluated through laser exposure on membrane-layered tumor cell lines, tumor xenograft-bearing mice. PDT with the Al-PcS4-integrated membrane successfully generated sufficient cytotoxic singlet oxygen, inducing cell death in the esophageal cancer cell lines. PDT-treated tumor xenograft-bearing mice undergo apoptotic cell death and showed significant tumor regression. Localized PDT using an Al-PcS4-integrated silicone-covered self-expanding catheter was technically successful in the rabbit esophagus without severe complications. Based on the endoscopy, esophagography, histology, and immunohistochemistry, our study verified that localized PDT using the Al-PcS4-integrated silicone-covered self-expanding catheter was effective and safe to evenly induce tissue damage. Al-PcS4-integrated silicone-covered self-expanding catheter has substantial potential for the minimally invasive local therapy in malignant esophageal cancer.

摘要

使用集成了光敏剂(PS)的覆膜自膨式金属支架(SEMS)进行光动力疗法(PDT)被提议作为一种治疗姑息性恶性肿瘤的新治疗方法;然而,目前的疏水性PS会降低光反应效果,导致其因低水溶性而聚集。在此,成功制造了一种集成了四磺酸铝酞菁氯(Al-PcS4)的硅胶覆膜自膨式导管,用于进行局部PDT。优化了甲醇与Al-PcS4浓度的比例,以实现PS涂层的均匀性。通过对膜层肿瘤细胞系、荷瘤异种移植小鼠进行激光照射,评估了集成Al-PcS4的硅胶膜的光动力活性。使用集成Al-PcS4的膜进行的PDT成功产生了足够的细胞毒性单线态氧,诱导食管癌细胞系中的细胞死亡。接受PDT治疗的荷瘤异种移植小鼠发生凋亡性细胞死亡,并显示出显著的肿瘤消退。在兔食管中,使用集成Al-PcS4的硅胶覆膜自膨式导管进行局部PDT在技术上是成功的,且无严重并发症。基于内镜检查、食管造影、组织学和免疫组织化学,我们的研究证实,使用集成Al-PcS4的硅胶覆膜自膨式导管进行局部PDT能有效且安全地均匀诱导组织损伤。集成Al-PcS4的硅胶覆膜自膨式导管在恶性食管癌的微创局部治疗方面具有巨大潜力。

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