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HDAC6-Activatable Multifunctional Near-Infrared Probe for Glioma Cell Detection and Elimination.

Wenyu Wei1,2, Chen Huang1,2, Jie Zhang1,3

  • 1Department of Chemistry and COSDAF (Centre of Super-Diamond and Advanced Films), City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, Hong Kong 999077, China.

Analytical Chemistry
|February 3, 2024
PubMed
Summary
This summary is machine-generated.

A new probe, HDAC-MB, detects and treats glioma by targeting histone deacetylase 6 (HDAC6) and monoamine oxidase A (MAO A). This multifunctional tool offers improved glioma diagnosis and therapy through imaging and synergistic treatment effects.

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Area of Science:

  • Biomedical Engineering
  • Molecular Oncology
  • Nanotechnology

Background:

  • Glioblastoma multiforme (GBM) presents significant therapeutic challenges due to its aggressive nature and drug resistance.
  • Epigenetic modifications, including histone deacetylase 6 (HDAC6) and monoamine oxidase A (MAO A) activity, are implicated in glioma progression and represent potential therapeutic targets.
  • Current treatment strategies for GBM are limited, necessitating the development of novel diagnostic and therapeutic approaches.

Purpose of the Study:

  • To engineer an activatable multifunctional small-molecule probe, HDAC-MB, for efficient glioma cell detection and eradication.
  • To investigate the capability of HDAC-MB to be selectively activated by HDAC6, leading to fluorescence and therapeutic effects.
  • To evaluate the synergistic therapeutic potential of HDAC-MB through MAO A inhibition and photodynamic therapy (PDT).

Main Methods:

  • Design and synthesis of HDAC-MB, a multifunctional small-molecule probe.
  • Assessment of HDAC-MB activation by HDAC6, resulting in near-infrared fluorescence.
  • Evaluation of HDAC-MB's efficacy in inhibiting MAO A and its photodynamic therapy (PDT) effects.
  • In vitro studies to assess glioma cell imaging, invasion inhibition, and apoptosis induction.

Main Results:

  • HDAC-MB was successfully engineered as an activatable probe.
  • Selective activation by HDAC6 led to "turn on" of near-infrared fluorescence, enabling imaging of HDAC6 in live glioma cells.
  • HDAC-MB demonstrated synergistic effects of MAO A inhibition and PDT, effectively inhibiting glioma invasion.
  • The probe induced significant cellular apoptosis in glioma cells.

Conclusions:

  • HDAC-MB serves as a versatile tool for the accurate diagnosis and treatment of glioma cells.
  • The probe's ability to combine imaging, MAO A inhibition, and PDT offers a synergistic therapeutic strategy.
  • HDAC-MB holds promise for enhancing glioma therapy outcomes and future theranostic applications.