研究概要
这种多功能贴片为晚期HCC患者提供了一种有前景的治疗策略。
中文摘要
复发和转移是肝细胞癌(HCC)死亡的主要原因,主要由免疫抑制性肿瘤微环境驱动。本研究开发了一种基于静电纺丝 SiO 2 凝胶纤维的多功能柔性贴片(MnO 2 -P-ICG NFs),其表面修饰有一层“巢状”MnO 2。该贴片能够通过腹腔镜系统将吲哚菁绿(ICG)和茯苓多糖直接共递送至肿瘤部位。在近红外光照射下,ICG 作为光动力疗法(PDT)的光敏剂,有效消融肿瘤并诱导免疫原性细胞死亡(ICD),从而激活抗肿瘤免疫。同时,茯苓多糖具有免疫调节作用,优先激活自然杀伤(NK)细胞以发挥抗肿瘤效应。此外,PDT 通过激活 cGAS-STING 通路进一步增强该免疫应答。在小鼠模型中,植入该贴片显著抑制了原发性肝脏肿瘤进展和腹水形成。在恶性肝脏肿瘤模型中,MnO 2 -P-ICG NFs 在 80% 的治疗小鼠中预防了局部复发。值得注意的是,NK 细胞耗竭和 cGAS-STING 通路阻断均会削弱 MnO 2 -P-ICG NFs 的治疗效果。在临床上,NK 细胞浸润较高的肿瘤与患者预后改善相关。总之,这种多功能贴片为晚期 HCC 患者提供了一种有前景的治疗策略。
展开英文摘要原文
Recurrence and metastasis are the primary causes of mortality in hepatocellular carcinoma (HCC), primarily driven by an immunosuppressive tumor microenvironment. This study developed a multifunctional flexible patch (MnO 2 -P-ICG NFs) based on electrospun SiO 2 gel fibers whose surface is modified with a layer of "nest-like" MnO 2 . The patch enables the co-delivery of indocyanine green (ICG) and pachymaran directly to the tumor site via a laparoscopic system. Under near-infrared light irradiation, ICG serves as a photosensitizer for photodynamic therapy (PDT), effectively ablating tumors and inducing immunogenic cell death (ICD), thereby activating antitumor immunity. Meanwhile, pachymaran, with its immunomodulatory effects, preferential activates natural killer (NK) cells to exert antitumor effects. Additionally, PDT further enhances this immune response by activating the cGAS-STING pathway. In mouse models, implantation of the patch significantly inhibited primary liver tumor progression and ascites formation. In a malignant liver tumor model, MnO 2 -P-ICG NFs prevented local recurrence in 80% of treated mice. Notably, both the depletion of NK cells and the blockade of the cGAS-STING pathway compromised the therapeutic efficacy of MnO 2 -P-ICG NFs. Clinically, tumors with higher NK cell infiltration were associated with improved patient outcomes. In conclusion, this versatile patch provides a promising therapeutic strategy for patients with advanced HCC.
论文信息
- 作者
- Lin J、Pan H、Wu K、Nan J、Dai J、Chang Y、Shen H、Ye Q
- 单位
- Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University, Hangzhou, China.China
- 期刊
- Advanced science (Weinheim, Baden-Wurttemberg, Germany)2026 Jun