药学学报, 2021, 56(11): 3060-3073
李聪, 范垂众, 闫鑫杨, 高新, 赖晓雪, 宋艳志, 刘欣荣, 邓意辉*. 唾液酸结合受体——令人瞩目的肿瘤治疗靶标[J]. 药学学报, 2021, 56(11): 3060-3073.
LI Cong, FAN Chui-zhong, YAN Xin-yang, GAO Xin, LAI Xiao-xue, SONG Yan-zhi, LIU Xin-rong, DENG Yi-hui*. Sialic acid binding receptors—impressive targets for tumor treatment[J]. Acta Pharmaceutica Sinica, 2021, 56(11): 3060-3073.

李聪, 范垂众, 闫鑫杨, 高新, 赖晓雪, 宋艳志, 刘欣荣, 邓意辉*
沈阳药科大学药学院, 辽宁 沈阳 110016
在肿瘤发展的各个阶段普遍存在着糖基化异常,其中唾液酸 (sialic acid,SA) 修饰聚糖在不同类型的肿瘤细胞表面显著高表达,这些高度唾液酸化的肿瘤细胞通过与外周免疫细胞或内皮细胞上的SA结合受体唾液酸结合性免疫球蛋白样凝集素 (sialic acid binding immunoglobulin-like lectins,Siglecs) 或选择素 (selectins) 相互作用,促进肿瘤免疫抑制环境的形成并帮助肿瘤细胞获得转移潜能。因此,针对Siglecs或selectins与其配体间相互作用的肿瘤治疗策略正受到研究者们的广泛关注,这些治疗策略主要包括靶向SA结合受体的特异性抗体吉妥珠单抗 (Mylotarg) 或聚糖类物质、SA及其衍生物修饰的纳米药物递送系统等。本文综述了Siglecs或selectins参与的促进肿瘤发展和转移过程的具体机制,以及靶向SA结合受体的肿瘤治疗策略,并对这些治疗策略进行了理性评价与反思。
关键词:    唾液酸      免疫学受体      肿瘤      特异性抗体      聚糖类物质      药物递送系统     
Sialic acid binding receptors—impressive targets for tumor treatment
LI Cong, FAN Chui-zhong, YAN Xin-yang, GAO Xin, LAI Xiao-xue, SONG Yan-zhi, LIU Xin-rong, DENG Yi-hui*
School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China
Glycosylation abnormalities are common in all stages of tumor development, and sialic acid (SA) modified polysaccharides have been found highly expressed on many different types of tumor cells. These highly sialylated tumor cells promote the formation of tumor immunosuppressive environment and help tumor cells gain metastatic potential by interacting with SA binding receptors Siglecs/selectins expressed on peripheral immune cells or endothelial cells. Related theoretical studies have promoted the development of tumor therapeutic strategies by targeting SA-binding receptors, mainly including specific antibodies trastuzumab (Mylotarg) or polysaccharides that block the interaction between Siglecs/selectins and its ligands, as well as nano-based drug delivery systems modified with SA and its derivatives. This article reviews the specific mechanisms of how SA-binding receptor Siglecs/selectins-mediated interactions contribute to tumor development and metastasis, and tumor therapeutic strategies by targeting SA-binding receptors, as well as makes a rational evaluation and reflection on these therapeutic strategies.
Key words:    sialic acid    immunologic receptor    neoplasm    anti-idiotypic antibody    glycosaminoglycan    drug delivery system   
收稿日期: 2021-04-13
DOI: 10.16438/j.0513-4870.2021-0543
基金项目: 国家自然科学基金资助项目(81973271).
通讯作者: 邓意辉,Tel:86-24-43520552,E-mail:pharmdeng@gmail.com
Email: pharmdeng@gmail.com
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李聪  在本刊中的所有文章
范垂众  在本刊中的所有文章
闫鑫杨  在本刊中的所有文章
高新  在本刊中的所有文章
赖晓雪  在本刊中的所有文章
宋艳志  在本刊中的所有文章
刘欣荣  在本刊中的所有文章
邓意辉*  在本刊中的所有文章

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