PDF(Pubmed)
Abstract：
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.
We describe the first enzyme‐activatable chemokine conjugates for selective targeting of tumor‐associated macrophages in preclinical models of cancer. We demonstrate that this new chemical design is compatible with both fluorescent and therapeutic payloads, opening avenues in the preparation of future theranostic probes for immune cells in the tumor microenvironment.
We describe the first enzyme‐activatable chemokine conjugates for selective targeting of tumor‐associated macrophages in preclinical models of cancer. We demonstrate that this new chemical design is compatible with both fluorescent and therapeutic payloads, opening avenues in the preparation of future theranostic probes for immune cells in the tumor microenvironment.
摘要：
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。尽管阻断巨噬细胞募集到肿瘤的抗体和小分子被评估为抗癌疗法，这些策略对巨噬细胞亚群没有特异性.在本文中，我们报告了第一个酶激活的趋化因子缀合物，用于有效靶向活肿瘤中确定的巨噬细胞亚群。我们的构建体利用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的活性选择性地靶向这些细胞而不是其他巨噬细胞和免疫细胞（例如，中性粒细胞，T细胞,B细胞）。此外，我们证明组织蛋白酶激活的趋化因子与荧光和治疗货物相容，为肿瘤微环境中的免疫细胞的靶向治疗诊断探针的设计开辟了新的途径。
我们描述了第一个酶激活的趋化因子缀合物，用于在癌症临床前模型中选择性靶向肿瘤相关巨噬细胞。我们证明了这种新的化学设计与荧光和治疗有效载荷兼容，为肿瘤微环境中的免疫细胞的未来治疗诊断探针的制备开辟了道路。
我们描述了第一个酶激活的趋化因子缀合物，用于在癌症临床前模型中选择性靶向肿瘤相关巨噬细胞。我们证明了这种新的化学设计与荧光和治疗有效载荷兼容，为肿瘤微环境中的免疫细胞的未来治疗诊断探针的制备开辟了道路。
