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Published on: December 15, 2010
Light-assisted gadofullerene nanoparticles disrupt tumor vasculatures for potent melanoma treatment
Zhigao Lu1, Wang Jia1, Ruijun Deng1
1Beijing National Laboratory for Molecular Sciences, Key Laboratory of Molecular Nanostructure and Nanotechnology, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China. zhenmm@iccas.ac.cn crwang@iccas.ac.cn and University of Chinese Academy of Sciences, Beijing 100049, China.
Abstract:
The traditional photodynamic therapy (PDT) using a photosensitizer and oxygen under light generates reactive oxygen species (ROS) to kill tumor cells. However, its treatment efficiency is limited by insufficient oxygen in tumor cells. Herein, β-alanine modified gadofullerene nanoparticles (GFNPs) were explored to disrupt tumor vasculatures assisted by light for potent melanoma treatment. As tumor vasculatures are oxygen-rich, the yields of photo-induced singlet oxygen (1O2) by GFNPs are not subjected to the hypoxemia of tumor tissues. Different from the small molecule photosensitizer Chlorin e6 (Ce6), GFNPs realize high-efficiency tumor vascular disruption under light observed by using the mice tumor vascular dorsal skin fold chamber (DSFC) model. The tumor vascular disruption efficiency of GFNPs is size-dependent, and the smallest one (hydration diameter of ca. 126 nm) is more efficient. Mechanistically, the high yields of photo-induced 1O2 by GFNPs can lead to the destruction of the tumor vascular endothelial adherent junction protein-VE cadherin and the decrease of tumor vascular endothelial cells-CD31 proteins, inducing rapid tumor necrosis. In conclusion, our work provides an insight into the design of well-sized nanoparticles to powerfully treat melanoma assisted by light, as well as greatly extending the applications of PDT for robust tumor therapy.
Insights
Gadolinium-based fullerene nanoparticles overcome oxygen deficiency in tumors by disrupting tumor vasculature with light. This photodynamic therapy approach effectively treats melanoma by generating singlet oxygen within oxygen-rich blood vessels.
Area of Science:
- Nanomedicine
- Photodynamic Therapy
- Cancer Research
Background:
- Traditional photodynamic therapy (PDT) efficacy is limited by tumor hypoxia, which reduces reactive oxygen species (ROS) generation.
- Developing oxygen-independent or oxygen-rich environment-targeting therapeutic strategies is crucial for effective cancer treatment.
Purpose of the Study:
- To investigate the potential of β-alanine modified gadofullerene nanoparticles (GFNPs) for light-activated disruption of tumor vasculature in melanoma treatment.
- To explore the size-dependent efficacy and mechanism of GFNPs in photodynamic therapy.
Main Methods:
- Utilized β-alanine modified gadofullerene nanoparticles (GFNPs) as photosensitizers.
- Employed a mice tumor vascular dorsal skin fold chamber (DSFC) model to observe tumor vascular disruption.
- Analyzed the effect of GFNPs on tumor vascular endothelial adherent junction protein-VE cadherin and CD31 expression.
Main Results:
- GFNPs effectively disrupted tumor vasculature under light, generating singlet oxygen (1O2) in oxygen-rich vascular environments, independent of tumor hypoxia.
- The smallest GFNPs (approx. 126 nm hydration diameter) demonstrated the highest tumor vascular disruption efficiency.
- GFNPs induced rapid tumor necrosis by damaging VE-cadherin and decreasing CD31 expression in tumor vascular endothelial cells.
Conclusions:
- Well-sized gadofullerene nanoparticles offer a potent strategy for melanoma treatment by leveraging light-activated tumor vascular disruption.
- This approach effectively overcomes the limitations of traditional PDT caused by tumor hypoxia, expanding PDT applications for robust cancer therapy.
