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高效合成叶绿素 e6 及其通过远隔效应在小鼠黑色素瘤中的潜在光动力免疫治疗。

Efficient Synthesis of Chlorin e6 and Its Potential Photodynamic Immunotherapy in Mouse Melanoma by the Abscopal Effect.

机构信息

Dongsung Cancer Center, Dongsung Biopharmaceutical, Daegu 41061, Republic of Korea.

出版信息

Int J Mol Sci. 2023 Feb 15;24(4):3901. doi: 10.3390/ijms24043901.

DOI:10.3390/ijms24043901
PMID:36835310
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9963834/
Abstract

Photodynamic therapy (PDT) can eradicate not only cancer cells but also stimulate an antitumor immune response. Herein, we describe two efficient synthetic methodologies for the preparation of Chlorin e6 (Ce6) from and address the phototoxic effect of Ce6 in vitro along with antitumor activity in vivo. Melanoma B16F10 cells were seeded and phototoxicity was monitored by the MTT assay. The C57BL/6 mice were subcutaneously inoculated on the left and right flank with B16F10 cells. The mice were intravenously injected with Ce6 of 2.5 mg/kg and then exposed to red light (660 nm) on the left flank tumors 3 h after the injection. The immune response was studied by analyzing Interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), and Interleukin-2 (IL-2) of the right flank tumors through qPCR. Our results revealed that the tumor was suppressed not only in the left flank but also in the right flank, where no PDT was given. The upregulated gene and protein expression of IFN-γ, TNF-α, and IL-2 revealed antitumor immunity due to Ce6-PDT. The findings of this study suggest an efficient methodology of Ce6 preparation and the efficacy of Ce6-PDT as a promising antitumor immune response.

摘要

光动力疗法 (PDT) 不仅可以消灭癌细胞,还可以刺激抗肿瘤免疫反应。在此,我们描述了两种从 制备氯(六)(Ce6)的高效合成方法,并探讨了 Ce6 的体外光毒性以及体内抗肿瘤活性。将黑色素瘤 B16F10 细胞播种,并通过 MTT 测定法监测细胞毒性。将 C57BL/6 小鼠的左侧和右侧肋部皮下接种 B16F10 细胞。小鼠静脉注射 2.5 mg/kg 的 Ce6,然后在注射后 3 小时在左侧肿瘤上暴露于红光(660nm)。通过 qPCR 分析右侧肿瘤中的干扰素-γ(IFN-γ)、肿瘤坏死因子-α(TNF-α)和白细胞介素-2(IL-2)来研究免疫反应。我们的结果表明,肿瘤不仅在左侧被抑制,而且在未进行 PDT 的右侧也被抑制。Ce6-PDT 引起 IFN-γ、TNF-α 和 IL-2 的基因和蛋白表达上调,揭示了抗肿瘤免疫。本研究的结果表明了 Ce6 制备的有效方法和 Ce6-PDT 作为一种有前途的抗肿瘤免疫反应的功效。

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