Molecularly engineered lipid droplet-targeted NIR-II type I AIE photosensitizers trigger ferroptosis and apoptosis for cancer therapy

IF 7.4 2区材料科学 Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY

Science China Materials Pub Date : 2025-08-07 DOI:10.1007/s40843-025-3483-5

Lijin Yang (, ), Jiabao Zhuang (, ), Jiawen Chen (, ), Xinrong Wu (, ), Nan Li (, ), Na Zhao (, )

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引用次数: 0

Abstract

Despite advancements in lipid droplet (LD)-targeted photosensitizers (PSs), critical challenges persist in achieving deep-tissue penetration, overcoming tumor hypoxic resistance, and coordinating multimodal cell death pathways. To address these limitations, a molecular engineering strategy was introduced to construct a series of aggregation-induced emission (AIE) PSs (MOITP, MOITM, and MOITT), which exhibited near-infrared (NIR) emission. The strong electron-withdrawing capability of the acceptor moiety in MOITT resulted in a bathochromic shift in absorption (606 nm) and NIR-II emission (1080 nm). Under 808 nm laser irradiation, MOITT exhibited the strongest type I reactive oxygen species generation and the highest photothermal conversion efficiency (η = 44%). Notably, MOITT nanoparticles (NPs) showed efficient cellular internalization and selective accumulation in LDs. Upon laser irradiation, phototherapy mediated by MOITT NPs initiated lipid peroxidation, triggering ferroptosis while synergistically inducing apoptosis. In vivo studies demonstrated that MOITT NPs enabled high-resolution NIR-II fluorescence imaging of blood vessels and effective imaging-guided phototherapy to eradicate tumors. This work establishes a novel paradigm for spatiotemporal control of cancer therapy through organelle-specific multimodal cell death integration.

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分子工程脂滴靶向NIR-II型AIE光敏剂引发铁凋亡和细胞凋亡用于癌症治疗

尽管脂滴（LD）靶向光敏剂（ps）取得了进展，但在实现深层组织渗透、克服肿瘤缺氧抵抗和协调多模式细胞死亡途径方面仍然存在关键挑战。为了解决这些问题，采用分子工程策略构建了一系列具有近红外发射特性的聚集诱导发射（AIE） ps （MOITP、MOITM和MOITT）。MOITT中受体部分的强吸电子能力导致了吸收（606 nm）和NIR-II发射（1080 nm）的色移。在808 nm激光照射下，MOITT的I型活性氧生成最强，光热转换效率最高（η = 44%）。值得注意的是，MOITT纳米颗粒（NPs）在ld中表现出高效的细胞内化和选择性积累。在激光照射下，MOITT NPs介导的光疗引发脂质过氧化，引发铁下垂，同时协同诱导细胞凋亡。体内研究表明，MOITT NPs能够实现血管的高分辨率NIR-II荧光成像和有效的成像引导光疗来根除肿瘤。这项工作通过细胞器特异性多模态细胞死亡整合为癌症治疗的时空控制建立了一个新的范例。

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来源期刊

Science China Materials Materials Science-General Materials Science

CiteScore

11.40

自引率

7.40%

发文量

949

期刊介绍： Science China Materials (SCM) is a globally peer-reviewed journal that covers all facets of materials science. It is supervised by the Chinese Academy of Sciences and co-sponsored by the Chinese Academy of Sciences and the National Natural Science Foundation of China. The journal is jointly published monthly in both printed and electronic forms by Science China Press and Springer. The aim of SCM is to encourage communication of high-quality, innovative research results at the cutting-edge interface of materials science with chemistry, physics, biology, and engineering. It focuses on breakthroughs from around the world and aims to become a world-leading academic journal for materials science.