智能响应, 精准点亮: 酶响应的聚集诱导发光材料在生物医学中的诊疗新策略
方瑾钰 , 黄瀚玮 , 宋航 , 吴谦 , 赵征 , 唐本忠
高等学校化学学报 ›› 2026, Vol. 47 ›› Issue (04) : 1 -20.
智能响应, 精准点亮: 酶响应的聚集诱导发光材料在生物医学中的诊疗新策略
Intelligent Response, Precision Activation: Novel Theranostic Strategies of Enzyme-responsive Aggregation-induced Emission Materials in Biomedicine
随着精准医学的发展, 对疾病实现高特异性、 高灵敏度的原位成像与靶向治疗提出了迫切需求. 传统荧光探针易受聚集诱导发光猝灭效应限制, 且常存在背景信号高、 光稳定性差、 特异性不足等问题. 聚集诱导发光材料因其单分子发光“熄灭”, 聚集体发光“点亮”的独特优势, 为构建性质优异的生物荧光探针提供了新思路. 酶作为疾病过程的关键生物标志物, 生物酶促反应具有底物专一、 高效等特性, 是聚集诱导发光材料在病灶部位实现可控响应、 荧光精准点亮与信号放大的理想触发机制. 本文综合评述了酶响应的聚集诱导发光材料在生物医学中的诊疗新策略这一前沿交叉领域的最新研究进展. 根据酶响应后聚集体形成的物理化学本质与结构特征, 系统梳理了三类分子设计策略, 重点阐述了其设计原理、 响应机制及其在各类重大疾病诊疗, 包括肿瘤成像与术中导航、 细菌与病毒感染诊疗、 神经退行性疾病诊断以及诊疗一体化等方面取得的显著成果. 酶响应的聚集诱导发光材料通过实现信号的可控“关-开”转换与靶向放大, 在提升成像信噪比、 治疗精准性和实现诊疗协同方面展现出巨大潜力. 最后, 对该领域当前面临的挑战进行了剖析, 并对未来发展趋势, 特别是与人工智能相结合的设计新范式进行了展望.
With the advancement of precision medicine, there is an urgent demand for in situ imaging and targeted therapy with high specificity and high sensitivity. Traditional fluorescent probes are often limited by aggregation-caused quenching effects and frequently suffer from issues such as high background signals, poor photostability, and insufficient specificity. Aggregation-induced emission(AIE) materials, with their unique characteristic of being “off”at the molecular level and “on” in the aggregated state, provide a new strategy for constructing high-performance biological fluorescent probes. Enzymes, serving as key biomarkers in disease processes, exhibit substrate specificity and high efficiency in biocatalytic reactions, making them an ideal trigger mechanism for achieving controllable response, precise fluorescence activation, and signal amplification at disease sites using AIE materials. This review comprehensively reviews the latest research progress in the interdisciplinary frontier of enzyme-responsive AIE materials for novel diagnostic and therapeutic strategies in biomedicine. Based on the physicochemical nature and structural characteristics of aggregates formed after enzyme response, we systematically categorize three molecular design strategies, with a focus on elucidating their design principles, response mechanisms, and significant achievements in the diagnosis and treatment of various major diseases, including tumor imaging and intraoperative navigation, diagnosis and treatment of bacterial and viral infections, diagnosis of neurodegenerative diseases, and theranostics. By enabling controllable “off-on” signal switching and targeted amplification, enzyme-responsive AIE materials demonstrate great potential in improving imaging signal-to-noise ratio, enhancing treatment precision, and achieving synergistic diagnosis and therapy. Finally, we analyze the current challenges in this field and provide an outlook on future development trends, particularly new design paradigms integrated with artificial intelligence.
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广东省高校创新团队计划(2025KCXTD054)
广东省重点领域研发计划项目(2024B0101040001)
深圳市 孔雀计划-孔雀团队:分子聚集体科学的基础理论及应用研究项目(KQTD20210811090142053)
深圳市 孔雀计划-孔雀团队:分子聚集体科学的基础理论及应用研究项目(2025GD0001)
广东省区域联合 基金-青年基金项目(2023A1515110346)
云南省重点研发计划(202303AC100010)
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