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Anticancer Efficacy of Photodynamic Therapy with Lung Cancer-Targeted Nanoparticles
Published on: December 1, 2016
Anticancer therapeutic effect of cerium-based nanoparticles: known and unknown molecular mechanisms
Maria John Newton Amaldoss1,2, Rashid Mehmood3, Jia-Lin Yang1
1Adult Cancer Program, Lowy Cancer Research Centre, Prince of Wales Clinical School, UNSW Sydney, Sydney, NSW 2052, Australia. m.amaldoss@unsw.edu.au.
Abstract:
Cerium-based nanoparticles (CeNPs), particularly cerium oxide (CeO2), have been studied extensively for their antioxidant and prooxidant properties. However, their complete redox and enzyme-mimetic mechanisms of therapeutic action at the molecular level remain elusive, constraining their potential for clinical translation. Although the therapeutic effects of both antioxidant and prooxidant mechanisms generally are attributed to Ce3+ ↔ Ce4+ redox switching mediation, some studies have hinted at the involvement of unknown pathways in therapeutic effects. While redox switching is recognised increasingly as playing a key role in ROS-dependent cancer therapy, ROS-independent cytotoxicity mechanisms, such as Ce4+ dissolution and autophagy, also are emerging as being of importance. Although ROS-mediated prooxidant therapies are the most intensively studied, particularly in the context of cancer, the antioxidant activity deriving from the redox switching, particularly during radiation therapy, also plays an important role in the protection of normal cells during radiation therapy, hence reducing adverse effects. Since cancer cell proliferation results in aberrant behaviour of the tumour microenvironment (TME), then CeNP-based therapies are being used to address a multiplicity of known and unknown factors that aim to normalise the TME and thus prevent this aberrant behaviour. Although it is perceived that the pH plays a key role in the therapeutic performance of cerium-based nanoparticles, this is not conclusive because the relative importances of other factors, particularly Ce dissolution, Ce3+/Ce4+ ratio, cellular H2O2 level, and the role of anions, remain poorly understood. Consequently, the present work explores these multiple chemistry-driven mechanisms, which are both ROS-dependent and ROS-independent, in cancer therapy.
Insights
Cerium-based nanoparticles (CeNPs) show promise in cancer therapy by leveraging antioxidant and prooxidant effects. This study investigates their complex redox and enzyme-mimetic mechanisms to improve clinical translation.
Area of Science:
- Nanomedicine
- Materials Science
- Biochemistry
Background:
- Cerium-based nanoparticles (CeNPs), especially cerium oxide (CeO2), possess dual antioxidant and prooxidant properties.
- The precise molecular mechanisms underlying their therapeutic action, including redox switching (Ce3+ ↔ Ce4+), remain incompletely understood, hindering clinical application.
- While reactive oxygen species (ROS)-dependent pathways are well-studied, ROS-independent mechanisms like Ce4+ dissolution and autophagy are gaining importance in cancer therapy.
Purpose of the Study:
- To elucidate the multifaceted, chemistry-driven mechanisms of cerium-based nanoparticles in cancer therapy.
- To explore both ROS-dependent and ROS-independent pathways contributing to therapeutic efficacy.
- To clarify the roles of factors such as Ce dissolution, Ce3+/Ce4+ ratio, and cellular H2O2 levels, beyond pH, in CeNP performance.
Main Methods:
- Exploration of redox switching (Ce3+ ↔ Ce4+) and its role in ROS-dependent and independent cancer therapy.
- Investigation of ROS-independent cytotoxicity mechanisms, including Ce4+ dissolution and autophagy.
- Analysis of the influence of various chemical factors (Ce dissolution, Ce3+/Ce4+ ratio, H2O2, anions) on CeNP therapeutic performance.
Main Results:
- Cerium-based nanoparticles exhibit complex therapeutic actions involving both antioxidant and prooxidant activities.
- Redox switching is crucial for ROS-dependent cancer therapy and normal cell protection during radiation therapy.
- Emerging evidence highlights the significance of ROS-independent mechanisms and specific chemical factors in CeNP efficacy.
Conclusions:
- Understanding the complete redox and enzyme-mimetic mechanisms of CeNPs is essential for their clinical translation in cancer treatment.
- Both ROS-dependent and ROS-independent pathways contribute to the therapeutic effects of CeNPs.
- Further research into factors like Ce dissolution and the Ce3+/Ce4+ ratio is needed to optimize CeNP-based cancer therapies and normalize the tumor microenvironment.
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