细胞因子诱导的杀伤细胞介导的氯素 e6 负载金纳米星用于肺癌的近红外靶向成像和免疫光动力联合疗法。

Chenlu Li, Zimei Liu, Zhonghua Cheng, Shuo Gu, Weiyong Zhao, Qian Zhang, Zhen Feng
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摘要

近年来,细胞因子诱导的杀伤细胞(CIK)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,我们报告了一种基于 PEG 化的单分散金纳米柱(GNSs)的简便合成策略,并与光敏剂氯素 e6(Ce6)共同负载形成 GNSs-PEG@Ce6 NPs。然后利用CIK细胞负载制备的GNSs-PEG@Ce6 NPs,制备出基于CIK细胞的肺癌给药系统(GNSs-PEG@Ce6-CIK)。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细胞作为免疫疗法的靶向载体,可提高肿瘤富集效率和治疗效果。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633 nm激光照射下可有效抑制A549细胞的生长,其杀伤作用强于GNSs-PEG@Ce6 NPs或CIK细胞。此外,它们在体内还表现出良好的肿瘤靶向性和肿瘤协同杀伤活性。因此,GNSs-PEG@Ce6-CIK被构建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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Cytokine-induced killer cells-mediated chlorin e6-loaded gold nanostars for targeted NIR imaging and immuno-photodynamic combination therapy for lung cancer.

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 activityin vivo. Therefore, GNSs-PEG@Ce6-CIK was constructed for targeted NIR fluorescence imaging, enhanced PDT and immunotherapy of lung cancer.

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