Chang Chun-Chun, Yang Chin-Hao, Chuang Chin-Hsien, Jiang Shinn-Jong, Hwang Yin-Min, Liou Je-Wen, Hsu Hao-Jen
Department of Laboratory Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, 97004, Taiwan, ROC.
Department of Laboratory Medicine and Biotechnology, College of Medicine, Tzu Chi University, Hualien, 97004, Taiwan, ROC.
Commun Chem. 2023 Dec 15;6(1):278. doi: 10.1038/s42004-023-01079-x.
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.
人白细胞介素-10(IL-10)是一种免疫抑制和抗炎细胞因子,在各种癌症患者的肿瘤组织和血清样本中其表达上调。由于其免疫抑制特性,IL-10也被认为是导致肿瘤细胞逃避宿主免疫系统免疫监视和清除的一个因素。在本研究中,我们基于对IL-10与IL-10受体的配体结合亚基IL-10Ra的复合物结构进行计算机模拟分析,优化了一种源自IL-10结合区域的20个氨基酸的肽,命名为NK20a。通过体外生物物理生物膜干涉术和细胞实验证实了该肽的结合能力。IL-10抑制肽对淋巴瘤B细胞具有抗癌作用,并且可以消除IL-10对巨噬细胞的抑制作用。NK20a还与金纳米颗粒偶联,靶向负载化疗药物5-氟尿嘧啶(5-FU)的纳米颗粒,以增强5-FU对乳腺癌细胞系BT-474的抗癌疗效。我们的研究表明,通过计算机模拟设计的与IL-10受体具有更高结合亲和力的NK20a可作为开发抗癌策略的一种工具。