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脂化纳米光敏剂通过追踪并抑制肿瘤胞外囊泡实现肿瘤生长与转移的同步阻断

Concurrent inhibition of tumor growth and metastasis by a lipidated nanophotosensitizer tracing and disabling tumor extracellular vesicles

原文发布日期：2025-06-24

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脂化纳米光敏剂通过追踪并抑制肿瘤胞外囊泡实现肿瘤生长与转移的同步阻断

Concurrent inhibition of tumor growth and metastasis by a lipidated nanophotosensitizer tracing and disabling tumor extracellular vesicles

原文发布日期：2025-06-24

英文摘要：

Cancer cells promote tumor growth and metastasis through tumor extracellular vesicle (TEV)-mediated intercellular and intertissue communication. Inhibiting TEVs represents a promising strategy to suppress metastasis; however, effectively and selectively disabling TEVs remains challenging. Herein, we developed palmitic acid surface-displayed nanoparticles using an adjacent hydrophilic molecular engineering strategy. Unexpectedly, these lipidated nanoparticles were not only efficiently taken up and distributed within tumor cells but also coupled with TEV generation, enabling active tracing of TEVs. Exploiting their dual tumor spatial distribution (intracellular and intra-TEV), a lipidated nanophotosensitizer was constructed for metastasis therapy. Under near-infrared light irradiation at the primary tumor site, both intracellular and intra-TEV reactive oxygen species were generated synchronously. This led to photodynamic suppression of the primary tumor and blocked intercellular and intertissue communication by disabling TEVs, effectively inhibiting tumor growth and metastasis in multiple tumor models in female mice. Overall, this work reports a therapeutic paradigm for concurrently inhibiting tumor growth and metastasis.

摘要翻译：

癌细胞通过肿瘤源性细胞外囊泡（TEV）介导的细胞间及组织间通讯促进肿瘤生长与转移。抑制TEV是一种极具前景的抗转移策略，然而如何高效、选择性地阻断TEV功能仍具挑战性。本研究采用邻位亲水分子工程策略开发了棕榈酸表面展示纳米颗粒。出乎意料的是，这些脂化纳米颗粒不仅能被肿瘤细胞高效摄取并在胞内分布，还可耦合TEV生成过程，实现对TEV的主动追踪。利用其在肿瘤空间的双重分布特性（细胞内与TEV内），我们构建了用于转移治疗的脂化纳米光敏剂。在原发灶近红外光照射下，细胞内与TEV内的活性氧同步生成，通过光动力作用抑制原发肿瘤的同时，还能通过破坏TEV阻断细胞间与组织间通讯，在雌性小鼠多种肿瘤模型中有效抑制了肿瘤生长与转移。本项研究为同步抑制肿瘤生长与转移提供了创新治疗范式。