中文摘要:
人白细胞介素 10 (IL-10) 是一种免疫抑制和抗炎细胞因子,其在各种癌症患者的肿瘤组织和血清样本中的表达上调。由于其免疫抑制性质,IL-10 也被认为是导致肿瘤细胞逃避免疫监视和宿主免疫系统清除的因素。在这项研究中,我们根据 IL-10 与 IL-10 受体的配体结合亚基 IL-10Ra 的复杂结构的计算机分析,提炼了一种具有 20 个氨基酸的肽,命名为 NK20a,来源于 IL-10 的结合区。通过体外生物物理生物膜干涉测量和细胞实验证实了肽的结合能力。IL-10 抑制肽对淋巴瘤 B 细胞发挥抗癌作用,可消除 IL-10 对巨噬细胞的抑制作用。NK20a 还与金纳米颗粒偶联以靶向化疗用 5-氟尿嘧啶 (5-FU) 负载的纳米颗粒,以增强 5-FU 对乳腺癌细胞系 BT-474 的抗癌功效。我们的研究表明,在计算机中设计的 NK20a 与 IL-10 受体的结合亲和力更高,可用作开发抗癌策略的工具。
英文摘要:
Human interleukin-10 (IL-10) is an immunosuppressive and anti-inflammatory cytokine, and its expression is upregulated in tumor tissues and serum samples of patients with various cancers. Because of its immunosuppressive nature, IL-10 has also been suggested to be a factor leading to tumor cells’ evasion of immune surveillance and clearance by the host immune system. In this study, we refined a peptide with 20 amino acids, named NK20a, derived from the binding region of IL-10 on the basis of in silico analysis of the complex structure of IL-10 with IL-10Ra, the ligand binding subunit of the IL-10 receptor. The binding ability of the peptide was confirmed through in vitro biophysical biolayer interferometry and cellular experiments. The IL-10 inhibitory peptide exerted anticancer effects on lymphoma B cells and could abolish the suppression effect of IL-10 on macrophages. NK20a was also conjugated with gold nanoparticles to target the chemotherapeutic 5-fluorouracil (5-FU)-loaded nanoparticles to enhance the anticancer efficacy of 5-FU against the breast cancer cell line BT-474. Our study demonstrated that NK20a designed in silico with improved binding affinity to the IL-10 receptor can be used as a tool in developing anticancer strategies.
论文信息:
论文题目: 源自白细胞介素 10 的肽具有潜在的抗癌活性,可促进载有抗癌治疗的金纳米颗粒的细胞靶向
期刊名称:Communications Chemistry
时间期卷: volume 6, Article number: 278 (2023)
在线时间:2023年12月15日
DOI: doi.org/10.1038/s42004-023-01079-x
悬浮细胞免疫荧光专用玻片Shi-Fix coverslips(靶点科技)见刊于Communications Chemistry:
悬浮细胞免疫荧光专用玻片Shi-Fix coverslips(靶点科技)见刊于Communications Chemistry:
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