Enzyme-Activatable Chemokine Conjugates for In Vivo Targeting of Tumor-Associated Macrophages
Enzyme-Activatable Chemokine Conjugates for In Vivo Targeting of Tumor-Associated Macrophages
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用于体内靶向肿瘤相关巨噬细胞的酶激活趋化因子缀合物
DOI：
10.1002/ange.202207508
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发表时间：
2022
影响因子：
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通讯作者：
Barth N
中科院分区：
文献类型：
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作者：
Barth N
肿瘤相关巨噬细胞（TAM）水平的增加是大多数癌症预后不良的指标。虽然阻断巨噬细胞向肿瘤募集的抗体和小分子正在被评估为抗癌疗法，但这些策略并不特异于巨噬细胞亚群。在本文中，我们报告了第一种酶活化趋化因子缀合物，用于有效靶向活肿瘤中定义的巨噬细胞亚群。我们的构建体利用了趋化因子受体的高表达（例如，CCR2）和TAM中半胱氨酸组织蛋白酶相对于其它巨噬细胞和免疫细胞（例如，嗜中性粒细胞、T细胞、B细胞）。此外，我们证明了组织蛋白酶活化趋化因子与荧光和治疗性货物相容，为肿瘤微环境中免疫细胞的靶向治疗诊断探针的设计开辟了新的途径。
Increased levels of tumor‐associated macrophages (TAMs) are indicators of poor prognosis in most cancers. Although antibodies and small molecules blocking the recruitment of macrophages to tumors are under evaluation as anticancer therapies, these strategies are not specific for macrophage subpopulations. Herein we report the first enzyme‐activatable chemokine conjugates for effective targeting of defined macrophage subsets in live tumors. Our constructs exploit the high expression of chemokine receptors (e.g., CCR2) and the activity of cysteine cathepsins in TAMs to target these cells selectively over other macrophages and immune cells (e.g., neutrophils, T cells, B cells). Furthermore, we demonstrate that cathepsin‐activatable chemokines are compatible with both fluorescent and therapeutic cargos, opening new avenues in the design of targeted theranostic probes for immune cells in the tumor microenvironment.