Specific Targeting, Imaging, and Ablation of Tumor-Associated Macrophages by Theranostic Mannose-AIEgen Conjugates.,Analytical Chemistry

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Specific Targeting, Imaging, and Ablation of Tumor-Associated Macrophages by Theranostic Mannose-AIEgen Conjugates.
Analytical Chemistry ( IF 6.7 ) Pub Date : 2019-04-22 00:00:00 , DOI: 10.1021/acs.analchem.9b01053
Xiaoying Gao _{1,

2} , Duo Mao ₂ , Xingang Zuo ₁ , Fang Hu ₂ , Jie Cao ₁ , Peng Zhang ₁ , Jing Zhi Sun ₁ , Jianzhao Liu ₁ , Bin Liu ₂ , Ben Zhong Tang _{1,

3,

4}

Affiliation

Tumor-associated macrophages (TAMs) that exist in tumor microenvironment promote tumor progression and have been suggested as a promising therapeutic target for cancer therapy in preclinical studies. Development of theranostic systems capable of specific targeting, imaging, and ablation of TAMs will offer clinical benefits. Here we constructed a theranostic probe, namely, TPE-Man, by attaching mannose moieties to a red-emissive and AIE (aggregation-induced emission)-active photosensitizer. TPE-Man can specifically recognize a mannose receptor that is overexpressed on TAMs by the sugar–receptor interaction and enables fluorescent visualization of the mannose-receptor-positive TAMs in high contrast. The histologic study of mouse tumor sections further verifies TPE-Man’s excellent targeting specificity being comparable with the commercial mannose-receptor antibody. TAMs can be effectively eradicated upon exposure to white light irradiation via a photodynamic therapy effect. To our knowledge, this is the first small molecular theranostic probe for TAMs that revealed combined advantages of low cost, high targeting specificity, fluorescent light-up imaging, and efficient photodynamic ablation.

中文翻译：

肿瘤相关的巨噬细胞的特定靶向，成像和消融的治疗性甘露糖-AIEgen结合。

存在于肿瘤微环境中的肿瘤相关巨噬细胞（TAM）促进肿瘤进展，并且在临床前研究中已被建议作为癌症治疗的有希望的治疗靶标。能够特异性靶向，成像和消融TAM的治疗治疗系统将提供临床益处。在这里，我们通过将甘露糖部分连接到红色发射和AIE（聚集诱导发射）活性光敏剂上，构建了一种治疗学探针，即TPE-Man。TPE-Man可以特异性识别通过糖-受体相互作用在TAM上过表达的甘露糖受体，并能以高对比度荧光显示甘露糖-受体阳性TAM。小鼠肿瘤切片的组织学研究进一步证实了TPE-Man的出色靶向特异性可与市售甘露糖受体抗体相媲美。通过光动力疗法作用，在暴露于白光照射下可以有效地消除TAM。据我们所知，这是第一款用于TAM的小分子治疗诊断探针，显示出低成本，高靶向特异性，荧光灯成像和有效的光动力消融相结合的优势。

更新日期：2019-04-22

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