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中文摘要:
人白細胞介素 10 (IL-10) 是一種免疫抑制和抗炎細胞因子,其在各種癌癥患者的腫瘤組織和血清樣本中的表達上調(diào)。由于其免疫抑制性質(zhì),IL-10 也被認為是導致腫瘤細胞逃避免疫監(jiān)視和宿主免疫系統(tǒng)清除的因素。在這項研究中,我們根據(jù) IL-10 與 IL-10 受體的配體結合亞基 IL-10Ra 的復雜結構的計算機分析,提煉了一種具有 20 個氨基酸的肽,命名為 NK20a,來源于 IL-10 的結合區(qū)。通過體外生物物理生物膜干涉測量和細胞實驗證實了肽的結合能力。IL-10 抑制肽對淋巴瘤 B 細胞發(fā)揮抗癌作用,可消除 IL-10 對巨噬細胞的抑制作用。NK20a 還與金納米顆粒偶聯(lián)以靶向化療用 5-氟尿嘧啶 (5-FU) 負載的納米顆粒,以增強 5-FU 對乳腺癌細胞系 BT-474 的抗癌功效。我們的研究表明,在計算機中設計的 NK20a 與 IL-10 受體的結合親和力更高,可用作開發(fā)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.
論文信息:
論文題目: 源自白細胞介素 10 的肽具有潛在的抗癌活性,可促進載有抗癌治療的金納米顆粒的細胞靶向
期刊名稱:Communications Chemistry
時間期卷: volume 6, Article number: 278 (2023)
在線時間:2023年12月15日
DOI: doi.org/10.1038/s42004-023-01079-x
懸浮細胞免疫熒光專用玻片Shi-Fix coverslips(靶點科技)見刊于Communications Chemistry:
懸浮細胞免疫熒光專用玻片Shi-Fix coverslips(靶點科技)見刊于Communications Chemistry:
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