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Updated: Oct 5, 2025
Intravital Microscopy of Tumor-associated Vasculature Using Advanced Dorsal Skinfold Window Chambers on Transgenic Fluorescent Mice
Published on: January 19, 2018
Anti-VEGFR2-labeled enzyme-immobilized metal-organic frameworks for tumor vasculature targeted catalytic therapy
Jingrong Zhou1, Kai Wang1, Shuaishuai Ding1
1Institute of Pathology and Southwest Cancer Center, The First Affiliated Hospital, and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Third Military Medical University (Army Medical University), Chongqing 40038, PR China.
Abstract:
Tumor vasculature-targeting therapy either using angiogenesis inhibitors or vascular disrupting agents offers an important new avenue for cancer therapy. In this work, a tumor-specific catalytic nanomedicine for enhanced tumor ablation accompanied with tumor vasculature disruption and angiogenesis inhibition was developed through a cascade reaction with enzyme glucose oxidase (GOD) modified on Fe-based metal organic framework (Fe-MOF) coupled with anti-VEGFR2.The GOD enzyme could catalyze the intratumoral glucose decomposition to trigger tumor starvation and yet provide abundant hydrogen peroxide as the substrate for Fenton-like reaction catalyzed by Fe-MOF to produce sufficient highly toxic hydroxyl radicals for enhanced chemodynamic therapy and instantly attacked tumor vascular endothelial cells to destroy the existing vasculature, while the anti-VEGFR2 antibody guided the nanohybrids to target blood vessels and block the VEGF-VEGFR2 connection to prevent angiogenesis. Both in vitro and in vivo results demonstrated the smart nanohybrids could cause the tumor cell apoptosis and vasculature disruption, and exhibited enhanced tumor regression in A549 xenograft tumor-bearing mice model. This study suggested that synergistic targeting tumor growth and its vasculature network would be more promising for curing solid tumors. STATEMENT OF SIGNIFICANCE: Cooperative destruction of tumor cells and tumor vasculature offers a potential avenue for cancer therapy. Under this premise, a tumor-specific catalytic nanomedicine for enhanced tumor ablation accompanied with tumor vasculature disruption and new angiogenesis inhibition was developed through a cascade reaction with glucose oxidase modified on the surface of iron-based metal organic framework coupled with VEGFR2 antibody. The resulting data demonstrated that a therapeutic regimen targeting tumor growth as well as its vasculature with both existing vasculature disruption and neovasculature inhibition would be more potential for complete eradication of tumors.
Insights
This study developed a novel nanomedicine that targets tumor cells and blood vessels, enhancing cancer therapy by disrupting tumor vasculature and inhibiting new blood vessel growth. The approach shows promise for more effective solid tumor treatment.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Therapy
Background:
- Tumor vasculature-targeting therapies, including angiogenesis inhibitors and vascular disrupting agents, represent a significant advancement in cancer treatment.
- Developing strategies that simultaneously target tumor cells and their vasculature is crucial for improving therapeutic outcomes.
Purpose of the Study:
- To develop a tumor-specific catalytic nanomedicine for enhanced tumor ablation.
- To achieve tumor vasculature disruption and angiogenesis inhibition through a cascade reaction.
- To evaluate the efficacy of this nanomedicine in vitro and in vivo.
Main Methods:
- A cascade reaction was designed using glucose oxidase (GOD) enzyme immobilized on an iron-based metal-organic framework (Fe-MOF).
- The nanomedicine was further functionalized with anti-VEGFR2 antibodies for targeted delivery.
- In vitro and in vivo studies were conducted using cancer cells and a xenograft tumor model in mice.
Main Results:
- The nanomedicine effectively catalyzed intratumoral glucose decomposition, producing hydrogen peroxide for Fenton-like reactions to generate hydroxyl radicals, leading to enhanced chemodynamic therapy.
- The system demonstrated immediate attack on tumor vascular endothelial cells, causing vasculature disruption.
- Anti-VEGFR2 antibodies guided targeting of blood vessels, blocking VEGF-VEGFR2 interaction and preventing angiogenesis.
- Significant tumor cell apoptosis and enhanced tumor regression were observed in the A549 xenograft tumor-bearing mice model.
Conclusions:
- Synergistic targeting of tumor growth and its vasculature network offers a promising strategy for solid tumor treatment.
- The developed nanomedicine demonstrates potential for enhanced tumor ablation by simultaneously disrupting existing vasculature and inhibiting angiogenesis.
- Cooperative destruction of tumor cells and tumor vasculature presents a viable therapeutic avenue for complete tumor eradication.
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