通过清道夫受体引导和组织蛋白酶B触发的纳米递送实现巨噬细胞重编程：从细胞内机制到转化应用
Macrophage reprogramming through scavenger receptor-guided and cathepsin B-triggered nanodelivery: from intracellular mechanisms to translational applications.
摘要(中文译文)
巨噬细胞是高度可塑的固有免疫细胞，其功能状态受炎症信号、代谢应激及疾病相关重塑的动态调控。在癌症和动脉粥样硬化中，病理性巨噬细胞参与免疫抑制、斑块不稳定化及治疗耐药，使其重编程成为关键的转化医学目标。纳米医学的最新进展通过将选择性细胞进入与条件性控制的细胞内释放相结合，为操控巨噬细胞行为提供了新机遇。本综述聚焦于清道夫受体引导和組織蛋白酶B触发的纳米递送系统，将其作为表型重塑的机制对齐策略。清道夫受体提供了在疾病相关巨噬细胞群体中富集的选择性分子入口，而組織蛋白酶B则作为后续纳米载体解组装和载荷释放的内源性触发器。我们讨论了如何通过协调靶向内吞与酶促释放来重塑巨噬细胞功能。我们还审视了这些平台如何介入细胞内脆弱性网络，重点突出信号转导与转录激活因子3（STAT3）作为一个具有转化相关性的节点——其稳定病理状态，而非作为唯一的机制轴心。最后，我们评估了主要的转化挑战，包括脱靶 sequestration、靶标异质性及功能性生物利用度。本综述旨在通过将纳米递送设计与巨噬细胞生物学及疾病相关细胞内机制相连接，推进以巨噬细胞为中心的免疫调节疗法的转化开发。
Abstract
Macrophages are highly plastic innate immune cells. Their functional states are dynamically shaped by inflammatory signals, metabolic stress, and disease-associated remodeling. In cancer and atherosclerosis, pathological macrophages contribute to immune suppression, plaque destabilization, and therapeutic resistance, making their reprogramming a critical translational goal. Recent advances in nanomedicine provide new opportunities to manipulate macrophage behavior by combining selective cellular entry with conditionally controlled intracellular release. This review focuses on scavenger receptor-guided and cathepsin B-triggered nanodelivery systems as a mechanism-aligned strategy for phenotypic remodeling. While scavenger receptors provide selective molecular gateways enriched in diseased macrophage populations, cathepsin B serves as an endogenous trigger for subsequent nanocarrier disassembly and payload release. We discuss how aligning targeted internalization and enzymatic release can reshape macrophage function. We also examine how these platforms engage intracellular vulnerability networks, highlighting signal transducer and activator of transcription 3 (STAT3) as a translationally relevant node that stabilizes pathological states rather than an exclusive mechanistic axis. Finally, we assess major translational challenges, including off-target sequestration, target heterogeneity, and functional bioavailability. This review aims to advance the translational development of macrophage-centered immunomodulatory therapies by linking nanodelivery design to macrophage biology and disease-relevant intracellular mechanisms.
如何引用
AMA
Yang Huang, Le Cai, Xu Yan, Kaiyi Tong, Fei Li. Macrophage reprogramming through scavenger receptor-guided and cathepsin B-triggered nanodelivery: from intracellular mechanisms to translational applications.. Frontiers in immunology. 2026; doi:10.3389/fimmu.2026.1879532.
APA
Yang Huang, Le Cai, Xu Yan, Kaiyi Tong, Fei Li (2026). Macrophage reprogramming through scavenger receptor-guided and cathepsin B-triggered nanodelivery: from intracellular mechanisms to translational applications.. Frontiers in immunology. https://doi.org/10.3389/fimmu.2026.1879532
GB/T 7714
Yang Huang, Le Cai, Xu Yan, Kaiyi Tong, Fei Li. Macrophage reprogramming through scavenger receptor-guided and cathepsin B-triggered nanodelivery: from intracellular mechanisms to translational applications.[J]. Frontiers in immunology, 2026 doi:10.3389/fimmu.2026.1879532.
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