HDAC6-Activatable Multifunctional Near-Infrared Probe for Glioma Cell Detection and Elimination,Analytical Chemistry

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HDAC6-Activatable Multifunctional Near-Infrared Probe for Glioma Cell Detection and Elimination
Analytical Chemistry ( IF 6.7 ) Pub Date : 2024-02-03 , DOI: 10.1021/acs.analchem.3c04319
Wenyu Wei _{1,

2} , Chen Huang _{1,

2} , Jie Zhang _{1,

3} , Qingxin Chen _{1,

2} , Zhiyang Liu _{1,

2} , Xiaojie Ren _{1,

2} , Shenglong Gan _{1,

2} , Pingzhou Wu _{1,

2} , Dongqing Wang _{1,

2} , Ben Zhong Tang ₄ , Hongyan Sun _{1,

2}

Affiliation

Glioblastoma multiforme (GBM) is a highly aggressive primary brain tumor associated with limited treatment options and high drug resistance, presenting significant challenges in the pursuit of effective treatment strategies. Epigenetic modifications have emerged as promising diagnostic biomarkers and therapeutic targets for GBM. For instance, histone deacetylase 6 (HDAC6) has been identified as a potential pharmacological target for GBM. Furthermore, the overexpression of monoamine oxidase A (MAO A) in glioma has been linked to tumor progression, making it an attractive target for therapy. In this study, we successfully engineered HDAC-MB, an activatable multifunctional small-molecule probe with the goal of efficiently detecting and killing glioma cells. HDAC-MB can be selectively activated by HDAC6, leading to the “turn on” of near-infrared fluorescence and effective inhibition of MAO A, along with potent photodynamic therapy (PDT) effects. Consequently, HDAC-MB not only enables the imaging of HDAC6 in live glioma cells but also exhibits the synergistic effect of MAO A inhibition and PDT, effectively inhibiting glioma invasion and inducing cellular apoptosis. The distinctive combination of features displayed by HDAC-MB positions it as a versatile and highly effective tool for the accurate diagnosis and treatment of glioma cells. This opens up opportunities to enhance therapy outcomes and explore future applications in glioma theranostics.

中文翻译：

HDAC6-可激活多功能近红外探针，用于神经胶质瘤细胞检测和消除

多形性胶质母细胞瘤（GBM）是一种高度侵袭性的原发性脑肿瘤，治疗选择有限且耐药性高，为寻求有效的治疗策略带来了重大挑战。表观遗传修饰已成为 GBM 有前途的诊断生物标志物和治疗靶点。例如，组蛋白脱乙酰酶 6 (HDAC6) 已被确定为 GBM 的潜在药理学靶点。此外，神经胶质瘤中单胺氧化酶 A (MAO A) 的过度表达与肿瘤进展有关，使其成为有吸引力的治疗靶点。在这项研究中，我们成功设计了HDAC-MB ，一种可激活的多功能小分子探针，旨在有效检测和杀死胶质瘤细胞。 HDAC-MB可以被 HDAC6 选择性激活，从而“开启”近红外荧光并有效抑制 MAO A，并产生有效的光动力疗法 (PDT) 效果。因此， HDAC-MB不仅能够在活胶质瘤细胞中对HDAC6进行成像，而且还表现出MAO A抑制和PDT的协同作用，有效抑制胶质瘤侵袭并诱导细胞凋亡。 HDAC-MB所显示的独特功能组合使其成为准确诊断和治疗神经胶质瘤细胞的多功能且高效的工具。这为增强治疗效果和探索神经胶质瘤治疗诊断学的未来应用提供了机会。

更新日期：2024-02-03

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