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 activityin vivo. Therefore, GNSs-PEG@Ce6-CIK was constructed for targeted NIR fluorescence imaging, enhanced PDT and immunotherapy of lung cancer.
摘要：
最近,细胞因子诱导的杀伤细胞(CIK)具有独特的杀伤和靶向恶性肿瘤的特点,在肿瘤的综合诊断和治疗中具有广阔的应用前景。在这里，我们报告了一种基于聚乙二醇化的单分散金纳米星（GNS）合成的简单策略，并与光敏剂二氢卟啉e6(Ce6)共负载以形成GNSs-PEG@Ce6NP。然后使用CIK细胞加载制备的GNSs-PEG@Ce6NP，制造基于aCIK细胞的肺癌药物递送系统(GNSs-PEG@Ce6-CIK)。其中,GNS用作传输介质，Ce6作为近红外（NIR）荧光显像剂和光动力疗法（PDT），和CIK细胞作为免疫疗法的靶向载体，可以提高肿瘤富集的效率和治疗效果。细胞实验结果表明GNSs-PEG@Ce6NPs具有良好的分散性,生理条件下的水溶性和低毒性，培养的CIK细胞具有较强的抗肿瘤特性。随后，GNSs-PEG@Ce6-CIK能有效抑制633nm激光照射下A549细胞的生长,显示出比GNSs-PEG@Ce6NPs或CIK细胞更强的杀伤作用。此外,它们在体内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被构建用于靶向NIR荧光成像，增强PDT和肺癌的免疫治疗。
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