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细胞因子诱导的杀伤细胞介导载氯乙啶的金纳米星用于肺癌的靶向近红外成像和免疫光动力联合治疗。

Cytokine-induced killer cells-mediated chlorin e6-loaded gold nanostars for targeted NIR imaging and immuno-photodynamic combination therapy for lung cancer.

机构信息

Department of Gastroenterology, Xuhui District Central Hospital of Shanghai, Shanghai 200031, People's Republic of China.

Department of Oncology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200050, People's Republic of China.

出版信息

Biomed Mater. 2024 Jun 25;19(4). doi: 10.1088/1748-605X/ad580c.

DOI:10.1088/1748-605X/ad580c
PMID:38870927
Abstract

Recently, cytokine-induced killer (CIK) cells have a broad application prospect in the comprehensive diagnosis and treatment of tumors owing to their unique characteristics of killing and targeting malignant tumors. Herein, we report a facile strategy for synthesis of monodisperse gold nanostars (GNSs) based on PEGylation and co-loaded with the photosensitizer chlorin e6 (Ce6) to form GNSs-PEG@Ce6 NPs. Then employing CIK cells loading the as-prepared GNSs-PEG@Ce6 NPs to fabricate a CIK cells-based drug delivery system (GNSs-PEG@Ce6-CIK) for lung cancer. Among them, GNSs was functioned as transport media, Ce6 acted as the near-infrared (NIR) fluorescence imaging agent and photodynamic therapy (PDT), and CIK cells served as targeting vectors for immunotherapy, which can increase the efficiency of tumor enrichment and treatment effect. The results of cellular experiments demonstrated that GNSs-PEG@Ce6 NPs had good dispersibility, water solubility and low toxicity under physiological conditions, and the cultured CIK cells had strong anti-tumor properties. Subsequently, GNSs-PEG@Ce6-CIK could effectively inhibit the growth of A549 cells under the exposure of 633 nm laser, which showed stronger killing effect than that of GNSs-PEG@Ce6 NPs or CIK cells. In addition, they showed good tumor targeting and tumor synergistic killing activity. Therefore, GNSs-PEG@Ce6-CIK was constructed for targeted NIR fluorescence imaging, enhanced PDT and immunotherapy of lung cancer.

摘要

近年来,细胞因子诱导的杀伤(CIK)细胞因其独特的杀伤和靶向恶性肿瘤的特性,在肿瘤的综合诊断和治疗中具有广阔的应用前景。在此,我们报道了一种基于聚乙二醇化和共载光敏剂氯代叶绿酸 e6(Ce6)形成金纳米星(GNSs)-PEG@Ce6 NPs 的单分散金纳米星(GNSs)的简便合成策略。然后,采用负载所制备的 GNSs-PEG@Ce6 NPs 的 CIK 细胞构建基于 CIK 细胞的药物传递系统(GNSs-PEG@Ce6-CIK)用于肺癌治疗。其中,GNSs 作为运输介质,Ce6 作为近红外(NIR)荧光成像剂和光动力疗法(PDT),CIK 细胞作为免疫治疗的靶向载体,可提高肿瘤富集和治疗效果的效率。细胞实验结果表明,GNSs-PEG@Ce6 NPs 在生理条件下具有良好的分散性、水溶性和低毒性,培养的 CIK 细胞具有很强的抗肿瘤特性。随后,GNSs-PEG@Ce6-CIK 在 633nm 激光照射下能有效抑制 A549 细胞的生长,其杀伤效果强于 GNSs-PEG@Ce6 NPs 或 CIK 细胞。此外,它们还表现出良好的肿瘤靶向性和肿瘤协同杀伤活性。因此,构建了 GNSs-PEG@Ce6-CIK 用于肺癌的靶向近红外荧光成像、增强 PDT 和免疫治疗。

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