Background: Reactive oxygen species (ROS) are powerful weapons for various anticancer therapies. However, high glutathione (GSH) levels in cancer cells can significantly reduce the efficacy of such therapies. Methods: In this study, pH-responsive fluorescein-encapsulated zeolitic imidazolate framework-8 nanoparticles were synthesized for ROS-mediated combination therapy. Results: Upon blue light activation, fluorescein displayed a high singlet oxygen photogeneration ability for photodynamic therapy. Concurrently, accumulated Zn²⁺ from degraded zeolitic imidazolate framework-8 stimulated simultaneous ROS generation and GSH depletion, thereby successfully inducing chemodynamic therapy. This triggered a cascade of photo–physical and chemical processes culminating in the localized generation of ROS, ultimately breaking the intracellular redox equilibrium. Conclusion: This nanoformulation can potentially be used for light-activated ROS-mediated therapy for the management of superficial tumors.

Plain language summary

Highly reactive molecules called reactive oxygen species (ROS) are known to be present in excess in cancer cells. As a result, cancer cells are more susceptible to death by any further rise in levels of these species. In the current study, fluorescein-encapsulated zeolitic imidazolate nanoparticles were prepared for blue light-activated ROS-enhancing combination therapy. The nanoparticles displayed significant toxicity against a breast cancer cell line and simultaneously induced glutathione depletion, an antioxidant known to reduce the efficacy of various cancer therapies. Thus, this study reveals the potential of fluorescein-encapsulated zeolitic imidazolate nanoparticles for light-activated ROS-mediated therapy for the treatment of superficial tumors.

Keywords:

Papers of special note have been highlighted as: • of interest; •• of considerable interest

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Vol. 18, No. 8

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Received 22 February 2023

Accepted 10 May 2023

Published online 2 June 2023

Published in print April 2023

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Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.futuremedicine.com/doi/suppl/10.2217/nnm-2023-0047

Author contributions

Work plan: A Mittal, AK Verma and I Roy; resource and fund generation: AK Verma and I Roy; experiments and data collection: A Mittal, M Yadav and L Biswas; data interpretation: A Mittal, M Yadav, L Biswas, AK Verma and I Roy; initial manuscript drafting: A Mittal, M Yadav and L Biswas; final manuscript editing: AK Verma and I Roy.

Financial & competing interests disclosure

This study was primarily supported by funding from the Major Research Project, Institution of Eminence, University of Delhi, India. A Mittal and L Biswas acknowledge fellowship support from the University Grants Commission, Government of India. M Yadav acknowledges fellowship support from the Council of Scientific and Industrial Research, Government of India. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

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