Citation: Tianheng Chen, Yanyu Zhang, Zhen Fang, Anze Liu, Yingxin Dong, Xiying Wu, Feng Yang, Huan Wang. Diphtheria toxin-derived short peptide enables dual targeted delivery of vorinostat for glioma treatment[J]. Chinese Chemical Letters, ;2026, 37(3): 111254. doi: 10.1016/j.cclet.2025.111254 shu

Diphtheria toxin-derived short peptide enables dual targeted delivery of vorinostat for glioma treatment

Tianheng Chen ^{a, 1} ,
Yanyu Zhang ^{b, 1} ,
Zhen Fang ^{a, 1} ,
Anze Liu ^c ,
Yingxin Dong ^c ,
Xiying Wu ^{d, *,} ,
Feng Yang ^{a, *,} ,
Huan Wang ^{c, e, *,}

a.
Department of Inorganic Chemistry, School of Pharmacy, Naval Medical University, Shanghai 200433, China
b.
Institute of Analytical Technology and Smart Instruments, Xiamen Key Laboratory of Food and Drug Safety, College of Environment and Public Health, Xiamen Huaxia University, Xiamen 361024, China
c.
Department of Pharmaceutical Sciences, School of Pharmacy, Naval Medical University, Shanghai 200433, China
d.
Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai 200433, China
e.
The Center for Basic Research and Innovation of Medicine and Pharmacy (MOE), School of Pharmacy, Naval Medical University, Shanghai 200433, China

wxyifd@163.com

yangfeng1008@126.com

wang568855641@163.com

Received Date: 10 February 2025
Revised Date: 20 April 2025
Accepted Date: 22 April 2025
Available Online: 23 April 2025

Figures(4)

Glioma, a highly aggressive brain tumor with a dismal prognosis, faces significant treatment hurdles due to the blood-brain barrier, which limits the efficient delivery of most medications. Diphtheria toxin receptor (DTR) is a specific receptor expressed both on brain microvascular endothelial cells and glioma, emerging as a potentially valuable target for targeted drug delivery system for glioma treatment. In this work, a short peptide (designated DTX) derived from diphtheria toxin, was rational designed and chemical synthesized based on the binding domain to DTR. The function of DTX as a ligand of DTR and the brain/glioma dual targeting efficacy were evaluated in vitro and in vivo. Furthermore, DTX was conjugated to vorinostat (SAHA) to enable its anti-glioma efficacy. The results demonstrated that DTX-SAHA can effectively cross the blood-brain barrier, exhibiting promising anti-glioma efficacy with good biocompatibility. This research confirmed the potential of DTX as the ligand for DTR-mediated intracranial drug delivery.
- Blood-brain barrier,
- Diphtheria toxin receptor,
- Glioma,
- Vorinostat,
- Peptide-drug conjugates
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