中文摘要:
人白細(xì)胞介素 10 (IL-10) 是一種免疫抑制和抗炎細(xì)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(dá)上調(diào)。由于其免疫抑制性質(zhì),IL-10 也被認(rèn)為是導(dǎo)致腫瘤細(xì)胞逃避免疫監(jiān)視和宿主免疫系統(tǒng)清除的因素。在這項(xiàng)研究中,我們根據(jù) IL-10 與 IL-10 受體的配體結(jié)合亞基 IL-10Ra 的復(fù)雜結(jié)構(gòu)的計(jì)算機(jī)分析,提煉了一種具有 20 個(gè)氨基酸的肽,命名為 NK20a,來(lái)源于 IL-10 的結(jié)合區(qū)。通過(guò)體外生物物理生物膜干涉測(cè)量和細(xì)胞實(shí)驗(yàn)證實(shí)了肽的結(jié)合能力。IL-10 抑制肽對(duì)淋巴瘤 B 細(xì)胞發(fā)揮抗癌作用,可消除 IL-10 對(duì)巨噬細(xì)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(fù)載的納米顆粒,以增強(qiáng) 5-FU 對(duì)乳腺癌細(xì)胞系 BT-474 的抗癌功效。我們的研究表明,在計(jì)算機(jī)中設(shè)計(jì)的 NK20a 與 IL-10 受體的結(jié)合親和力更高,可用作開(kāi)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(xì)胞介素 10 的肽具有潛在的抗癌活性,可促進(jìn)載有抗癌治療的金納米顆粒的細(xì)胞靶向
期刊名稱(chēng):Communications Chemistry
時(shí)間期卷: volume 6, Article number: 278 (2023)
在線時(shí)間:2023年12月15日
DOI: doi.org/10.1038/s42004-023-01079-x
懸浮細(xì)胞免疫熒光專(zhuān)用玻片Shi-Fix coverslips(靶點(diǎn)科技)見(jiàn)刊于Communications Chemistry:
懸浮細(xì)胞免疫熒光專(zhuān)用玻片Shi-Fix coverslips(靶點(diǎn)科技)見(jiàn)刊于Communications Chemistry:
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