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Catalytic Scavenging of Plant Reactive Oxygen Species In Vivo by Anionic Cerium Oxide Nanoparticles
Published on: August 26, 2018
ROS-Mediated Anti-Angiogenic Activity of Cerium Oxide Nanoparticles in Melanoma Cells
Joel M Yong1, Lu Fu1, Fengying Tang1,2
1Graduate School of Biomedical Engineering, Level 5, Samuels Building, UNSW Sydney, Sydney, NSW 2052, Australia.
Abstract:
Angiogenesis plays a key role in cancer progression, including transition to the metastatic phase via reactive oxygen species (ROS)-dependent pathways, among others. Antivascular endothelial growth factor (VEGF) antibodies have been trialed as an anti-angiogenic therapy for cancer but are associated with high cost, limited efficacy, and side effects. Cerium oxide nanoparticles (nanoceria) are promising nanomaterials for biomedical applications due to their ability to modulate intracellular ROS. Nanoceria can be produced by a range of synthesis methods, with chemical precipitation as the most widely explored. It has been reported that chemical precipitation can fine-tune primary particle size where a limited number of synthesis parameters were varied. Here, we explore the effect of temperature, precipitating agent concentration and rate of addition, stirring rate, and surfactant concentration on nanoceria primary particle size using a fractional factorial experimental design approach. We establish a robust synthesis method for faceted nanoceria with primary particle diameters of 5-6 nm. The nanoceria are not cytotoxic to a human melanoma cell line (Mel1007) at doses up to 400 μg/mL and are dose-dependently internalized by the cells. The intracellular ROS level for some cells that internalized the nanoceria is reduced, which correlates with a dose-dependent reduction in angiogenic gene expression including VEGF. These findings contribute to our knowledge of the anti-angiogenic effects of nanoceria and help to develop our understanding of potentially new anti-angiogenic agents for combination cancer therapies.
Insights
Cerium oxide nanoparticles (nanoceria) effectively reduce reactive oxygen species (ROS) and inhibit angiogenesis in cancer cells. This study optimized nanoceria synthesis for potential use as a novel anti-cancer therapy.
Area of Science:
- Biomedical Nanotechnology
- Cancer Biology
- Materials Science
Background:
- Angiogenesis, driven by reactive oxygen species (ROS), is crucial for cancer progression and metastasis.
- Current anti-angiogenic therapies like anti-VEGF antibodies face limitations in efficacy, cost, and side effects.
- Cerium oxide nanoparticles (nanoceria) show potential for modulating ROS in biomedical applications.
Purpose of the Study:
- To optimize the synthesis of cerium oxide nanoparticles (nanoceria) for controlled primary particle size.
- To investigate the anti-angiogenic effects of synthesized nanoceria on a human melanoma cell line.
- To explore nanoceria as a potential component of novel combination cancer therapies.
Main Methods:
- Utilized a fractional factorial experimental design to study the impact of synthesis parameters (temperature, precipitating agent concentration/rate, stirring rate, surfactant concentration) on nanoceria particle size.
- Synthesized faceted nanoceria with primary particle diameters of 5-6 nm.
- Assessed nanoceria cytotoxicity, cellular internalization, intracellular ROS modulation, and angiogenic gene expression (including VEGF) in Mel1007 melanoma cells.
Main Results:
- Established a robust synthesis method yielding nanoceria with controlled 5-6 nm primary particle size.
- Demonstrated that nanoceria are non-cytotoxic to Mel1007 cells at doses up to 400 μg/mL.
- Observed dose-dependent internalization of nanoceria, leading to reduced intracellular ROS and a correlated dose-dependent decrease in angiogenic gene expression, including VEGF.
Conclusions:
- Optimized nanoceria synthesis provides a tunable platform for potential anti-cancer therapeutics.
- Nanoceria exhibit promising anti-angiogenic properties by reducing ROS and inhibiting key angiogenic factors like VEGF.
- These findings support the development of nanoceria as a novel therapeutic agent for combination cancer treatments.
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01:10Mechanism of Angiogenesis