2. Academic Validation
  3. In Situ Ferroptosis with Global Dynamics Visualization for Glioblastoma Theranostics

In Situ Ferroptosis with Global Dynamics Visualization for Glioblastoma Theranostics

  • J Med Chem. 2025 Dec 11;68(23):25307-25323. doi: 10.1021/acs.jmedchem.5c02290.
Rajneesh Mungur 1,  Ping Han 2,  Jun Gu 1,  Kaixin Zhang 3,  Xueyun Zhang 4 5 6,  Mahanand Chatoo 7,  Yuxia Liu 8,  Rui Shi 1,  Haifeng He 1,  Yindan Lin 4 5,  Min Yan 1,  Feng Xiao 1,  Zebin Fang 1,  Yuxiang Weng 1,  Kaiyuan Huang 1,  Ping Lan 1,  Jiesheng Zheng 1,  Ying Tong 1,  Linchun Jin 1,  Ben Wang 4 9 10 11 12 13,  Guang Chen 8,  Renya Zhan 1
Affiliations

Affiliations

  • 1 Department of Neurosurgery, The First Affiliated Hospital of School of Medicine, Zhejiang University, Hangzhou 310003, China.
  • 2 College of Chemistry and Chemical Engineering, Qufu Normal University, Qufu 273165, China.
  • 3 Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China.
  • 4 Cancer Institute (key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.
  • 5 Department of Biochemistry, Zhejiang University School of Medicine, Hangzhou 310058, China.
  • 6 School of Medicine, Taizhou University, Taizhou, Zhejiang 318000 China.
  • 7 School of Brain Science and Brain Medicine, Zhejiang University, Hangzhou 310058, China.
  • 8 College of Chemistry and Chemical Engineering, Shaanxi Key Laboratory of Chemical Additives for Industry, Shaanxi University of Science and Technology, Xi'an 710021, China.
  • 9 Institute of Translational Medicine, Zhejiang University, Hangzhou 310029, China.
  • 10 Institute of Fundamental and Transdisciplinary Research, Zhejiang University, Hangzhou 310027, China.
  • 11 Zhejiang Key Laboratory of Frontier Medical Research on Cancer Metabolism, Hangzhou 310029, China.
  • 12 Cancer Center, Zhejiang University, Hangzhou 310029, China.
  • 13 State Key Laboratory of Transvascular Implantation Devices, Hangzhou 310009, China.
PMID: 41267343 DOI: 10.1021/acs.jmedchem.5c02290
Abstract

Glioblastoma Multiforme (GBM) remains a lethal Cancer due to its invasive nature and limited treatment options. We present 1-ethyl-2-((E)-2-((E)-3-(2-((E)-1-ethyl-3,3-dimethylindolin-2-ylidene)ethylidene)-2-(4-(6-methyl-4,8-dioxo-1,3,6,2-dioxazaborocan-2-yl)phenoxy)cyclohex-1-en-1-yl)vinyl)-3,3-dimethyl-3H-indol-1-ium (CDI), a near-infrared (NIR) activatable theranostic probe that integrates tumor detection, in situ Ferroptosis induction, and treatment monitoring. CDI selectively activates in the GBM tumor microenvironment (H2O2 >30 μM) via boronate ester cleavage, enabling precise Cancer discrimination. Upon activation, CDI releases diacetic acid (MDA) that chelates endogenous Fe3+ in situ, driving localized Fenton reactions to induce Ferroptosis without systemic iron supplementation. A concurrent ratiometric fluorescence shift (675 → 750 nm) provides potential real-time feedback on treatment efficacy. Transcriptomic analysis verified Ferroptosis as the primary cell death mechanism, with significant dysregulation of iron/lipid metabolism pathways. In vitro and in vivo studies demonstrated blood-brain barrier (BBB) penetration, tumor-specific accumulation, inhibition of glioma cell migration/invasion, and extended survival in GBM models with no major adverse effects. CDI establishes a transformative "see-treat-confirm" paradigm for GBM surgery.

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