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三层功能聚合物材料作为药物载体治疗原位结肠癌的疗效。

The treatment efficacy of three-layered functional polymer materials as drug carrier for orthotopic colon cancer.

机构信息

Department of Gastrointestinal Colorectal & Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun, China.

Department of Anesthesiology, Jilin Cancer Hospital, Changchun, China.

出版信息

Drug Deliv. 2022 Dec;29(1):2971-2983. doi: 10.1080/10717544.2022.2122633.

Abstract

Colorectal cancer (CRC) is a worldwide disease posing serious threats to people's life. Surgery and postsurgical chemotherapy are still the first choices to control the rapid progression of cancer. However, tumor recurrence and even distant metastasis are prone to occur. As a result, it is in urgent demand to find a new method to control CRC progression while inhibiting distant metastasis. On this basis, this study developed the three-layered functionalized hydrogel-fibrous membrane-hydrogel composite materials. The Chinese traditional drugs 20 (S)-ginsenoside Rg3 (Rg3) and chemotherapeutic agent 5-fluorouracil (5-Fu) were loaded in the inner hydrogel and middle fibrous membrane and could be constantly released at the same time and space. The outer hydrogel was decorated with phenylboronic acid (PA) to interact with sialic acid expressed on the CRC cell surface. The composite materials possessed biocompatibility and showed no toxicity to normal human intestinal mucosa endothelial cells HIEC. According to the results, the cell viability of CT26 could be significantly decreased . The three-layered functionalized materials inhibited the original tumor progression and distant tumor metastasis to the liver in an orthotopic colon cancer mouse model by increasing the caspase3 expression and inhibiting the expressions of Bcl-2, Ki-67, and VEGF. In addition, the functions of major organs were not significantly damaged. Our study provides a safe and efficacious method of this three-layered functionalized hydrogel-fibrous membrane-hydrogel composite materials for CRC treatment.

摘要

结直肠癌(CRC)是一种全球性疾病,对人们的生命构成严重威胁。手术和术后化疗仍然是控制癌症快速进展的首选方法。然而,肿瘤复发甚至远处转移仍然容易发生。因此,迫切需要找到一种新的方法来控制 CRC 的进展,同时抑制远处转移。在此基础上,本研究开发了三层功能化水凝胶纤维膜水凝胶复合材料。将中药 20(S)-人参皂苷 Rg3(Rg3)和化疗药物 5-氟尿嘧啶(5-Fu)装载在内水凝胶和中纤维膜中,可以同时和空间持续释放。外水凝胶用苯硼酸(PA)修饰,与 CRC 细胞表面表达的唾液酸相互作用。该复合材料具有生物相容性,对正常人肠黏膜内皮细胞 HIEC 没有毒性。结果表明,CT26 的细胞活力明显降低。三层功能化材料通过增加 caspase3 的表达和抑制 Bcl-2、Ki-67 和 VEGF 的表达,抑制原位肿瘤的进展和远处肿瘤转移到肝脏,在原位结肠癌小鼠模型中。此外,主要器官的功能没有明显受损。我们的研究为 CRC 的治疗提供了一种安全有效的三层功能化水凝胶纤维膜水凝胶复合材料的方法。

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