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肝癌衍生蛋白包裹的氧化铁/黑磷纳米片用于靶向光热化疗。

Hepatocellular carcinoma-derived protein encapsulated iron oxide/black phosphorus nanosheets for targeted photothermal-chemotherapy.

作者信息

Yan Danhong, Guo Chaiqiong, Wang Yang, Wei Yan

机构信息

Department of Medical Technology, Suzhou Chien-shiung Institute of Technology, Taicang 215411, Jiangsu Province, People's Republic of China.

Department of Biomedical Engineering, Research Center for Nano-Biomaterials & Regenerative Medicine, College of Artificial Intelligence, Taiyuan University of Technology, Taiyuan 030024, People's Republic of China.

出版信息

Biomed Mater. 2025 Jul 15;20(4). doi: 10.1088/1748-605X/adebd1.

DOI:10.1088/1748-605X/adebd1
PMID:40609604
Abstract

In cancer treatment, single modalities such as chemotherapy or photothermal therapy (PTT) often face significant limitations, leading to suboptimal therapeutic outcomes. In recent years, the combination of chemotherapy and PTT has garnered significant attention as a promising approach for enhancing cancer treatment efficacy. In this study, we designed a nanodrug delivery system based on black phosphorus nanosheets (BPNS) and FeOcomposites, incorporating molecular and magnetic targeting strategies. The system loaded the small-molecule anticancer drug RSL3 and was encapsulated with hepatocellular carcinoma cell membrane proteins to form the Pro@FeO/BPNS-RSL3 composite nanosystem. The goal was to enhance targeted chemo-photothermal combination therapy. The physical and chemical properties, photothermal performance and stability, drug release kinetics,cellular uptake, cell compatibility, and synergistic therapeutic effects were all evaluated. The results demonstrated that the composite nanosystem exhibited excellent photothermal performance and stability. After 72 h at pH 5.5, the cumulative release of RSL3 reached 69.93%, indicating a faster and higher drug release profile under acidic conditions.cell uptake experiments showed significantly higher uptake by liver cancer cells (Huh7) compared to normal cells (LO2), suggesting that the system effectively targets liver cancer cells. Additionally,synergistic therapeutic results revealed that the composite nanosystem reduced the survival rate of liver cancer cells to less than 15%. Western blot analysis further confirmed that the system downregulated the expression of FACL4, Ferritin, and GPX4, thereby promoting the ferroptosis of cancer cells. Overall, the findings highlight that this nanosystem exhibits remarkable cancer cell-killing effects and offers a promising novel strategy for tumor therapy. Its potential for application in cancer treatment is significant, providing a new avenue for more effective and targeted therapies.

摘要

在癌症治疗中,单一治疗方式如化疗或光热疗法(PTT)往往面临显著局限性,导致治疗效果欠佳。近年来,化疗与PTT的联合作为一种有望提高癌症治疗效果的方法受到了广泛关注。在本研究中,我们基于黑磷纳米片(BPNS)和FeO复合材料设计了一种纳米药物递送系统,结合了分子靶向和磁靶向策略。该系统负载小分子抗癌药物RSL3,并包裹肝细胞癌细胞膜蛋白,形成Pro@FeO/BPNS-RSL3复合纳米系统。目的是增强靶向化学-光热联合治疗效果。对其物理化学性质、光热性能和稳定性、药物释放动力学、细胞摄取、细胞相容性以及协同治疗效果进行了评估。结果表明,该复合纳米系统表现出优异的光热性能和稳定性。在pH 5.5条件下72小时后,RSL3的累积释放率达到69.93%,表明在酸性条件下药物释放更快且更高。细胞摄取实验显示,与正常细胞(LO2)相比,肝癌细胞(Huh7)对该系统的摄取显著更高,这表明该系统能有效靶向肝癌细胞。此外,协同治疗结果显示,复合纳米系统将肝癌细胞的存活率降低至15%以下。蛋白质免疫印迹分析进一步证实,该系统下调了FACL4、铁蛋白和GPX4的表达,从而促进癌细胞的铁死亡。总体而言,研究结果表明该纳米系统具有显著的癌细胞杀伤作用,为肿瘤治疗提供了一种有前景的新策略。其在癌症治疗中的应用潜力巨大,为更有效、更具靶向性的治疗提供了新途径。

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