Sialic Acids Blockade-Based Chemo-Immunotherapy Featuring Cancer Cell Chemosensitivity and Antitumor Immune Response Synergies

文献类型： 外文期刊

第一作者： Zhang, Xiang

作者： Zhang, Xiang;Li, Zi-Yi;Xiao, Jia-Heng;Mo, Juan;Zheng, Xiu-Jing;Ye, Xin-Shan;Zhang, Xiang;Li, Zi-Yi;Xiao, Jia-Heng;Mo, Juan;Zheng, Xiu-Jing;Ye, Xin-Shan;Hao, Peng-Fei;Geng, Yi-Qun

作者机构：

关键词： antitumor immune response; chemo-immunotherapy; chemosensitivity; sialic acid; sialyltransferase inhibitor

期刊名称：ADVANCED HEALTHCARE MATERIALS （ 影响因子：10.0； 五年影响因子：11.3 ）

ISSN： 2192-2640

年卷期： 2024 年

页码：

收录情况： SCI

摘要： Immune checkpoint blockade (ICB) has significantly improved the prognosis of patients with cancer, although the majority of such patients achieve low response rates; consequently, new therapeutic approaches are urgently needed. The upregulation of sialic acid-containing glycans is a common characteristic of cancer-related glycosylation, which drives disease progression and immune escape via numerous pathways. Herein, the development of self-assembled core-shell nanoscale coordination polymer nanoparticles loaded with a sialyltransferase inhibitor, referred to as NCP-STI which effectively stripped diverse sialoglycans from cancer cells, providing an antibody-independent pattern to disrupt the emerging Siglec-sialic acid glyco-immune checkpoint is reported. Furthermore, NCP-STI inhibits sialylation of the concentrated nucleoside transporter 1 (CNT1), promotes the intracellular accumulation of anticancer agent gemcitabine (Gem), and enhances Gem-induced immunogenic cell death (ICD). As a result, the combination of NCP-STI and Gem (NCP-STI/Gem) evokes a robust antitumor immune response and exhibits superior efficacy in restraining the growth of multiple murine tumors and pulmonary metastasis. Collectively, the findings demonstrate a novel form of small molecule-based chemo-immunotherapy approach which features sialic acids blockade that enables cooperative effects of cancer cell chemosensitivity and antitumor immune responses for cancer treatment. Nanoscale coordination polymer nanoparticles carrying a sialyltransferase inhibitor (NCP-STI) are constructed, which not only provide an antibody-independent pattern for disruption the Siglec-sialic acid glyco-immune checkpoint, but also enhance the chemosensitivity as well as immunogenic cell death of tumor cells to gemcitabine. The development of NCP-STI offers an effective antibody-free chemo-immunotherapy paradigm and may find broad applications in cancer treatment. image

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