posted on 2024-02-03, 14:03authored byWenyu Wei, Chen Huang, Jie Zhang, Qingxin Chen, Zhiyang Liu, Xiaojie Ren, Shenglong Gan, Pingzhou Wu, Dongqing Wang, Ben Zhong Tang, Hongyan Sun
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.