Multifunctional carbon quantum dots as a theranostic nanomedicine for fluorescence imaging-guided glutathione depletion to improve chemodynamic therapy

doi:10.1016/j.jcis.2021.08.114

Journal of Colloid and Interface Science

Volume 606, Part 2, 15 January 2022, Pages 1219-1228

https://doi.org/10.1016/j.jcis.2021.08.114 Get rights and content

Abstract

To minimize unwanted reactions with high concentrations of reduced glutathione (GSH) in the tumor microenvironment (TME) during chemodynamic therapy (CDT), a simple and effective strategy was developed to fabricate a TME stimuli-responsive theranostic nanomedicine (Fe-CD) for fluorescence imaging-guided GSH depletion and cancer therapy by combining fluorescent imaging carbon dots (CD) and Fe(III). Introducing Fe(III) into Fe-CD not only quenched the fluorescence of CD while reacting with and consuming intracellular GSH for fluorescence imaging of the depletion of GSH but also provided a source of metal ions to generate more abundant hydroxyl radicals (•OH) with hydrogen peroxide (H₂O₂) through the Fenton reaction to improve CDT. Fe-CD showed promising •OH generation under H₂O₂ to effectively degrade methylene blue in vitro and obviously activate the green fluorescence of the reactive oxygen species (ROS) probe in cells. Benefiting from the fluorescence enhancement in response to TME stimulation, Fe-CD greatly enhanced CDT cytotoxicity while monitoring successful GSH depletion by fluorescence imaging. Fe-CD has the potential to act as a theranostic nanomedicine for fluorescence imaging-guided GSH depletion to amplify CDT.

Graphical abstract

Section snippets

1. Introduction

Cancer is a series of complex diseases that lead to uncontrolled cell growth and death and that have the ability to escape the body's natural cellular mechanisms [1], [2]. Recent statistics have shown a significant increase in cancer-related mortality [3]. The current mainstream cancer treatments (such as surgery, chemotherapy and radiation therapy) show only limited results in terms of curing cancer. There is an urgent need for advanced cancer therapeutic strategies with improved efficacy and

Materials and methods

Unless otherwise stated, all compounds and reagents were purchased and used directly without purification. Glycerol (EP, BP, USP grade), ferric chloride (98%), glutathione (98%), N-[3-(trimethoxysilyl)propyl]ethylenediamine (95%, DAMO), and 5,5-dimethyl-1-pyrroline N-oxide (97%, DMPO) were purchased from Aladdin Reagent (Shanghai, China). Methylene blue (98.5%, MB) was ordered from Chengdu Kelon Chemical Reagent Factory. Both 1640 medium and foetal bovine serum (FBS) were obtained from

Synthesis of Fe-CD

In this study, we introduced a facile method of using CD and iron ion complexes for CDT as shown in Fig. 1A. First, CD was prepared by a solvothermal method. It has been reported that specific covalent binding occurs between Fe(III) and amine groups as well as hydroxyl groups.[44], [45] Inspired by this, we deduced that Fe(III) could be modified effectively to obtain a complex (Fe-CD) coordinated with amino and hydroxyl groups on the surface of CD. CD was selected because of the nature of the

Conclusions

In summary, we applied an “off–on” detection strategy to the nanomedicine field for fluorescence imaging-guided reduced glutathione (GSH) depletion to improve chemodynamic therapy (CDT). A facile strategy was developed to fabricate tumor microenvironment (TME) stimuli-responsive theranostic nanomedicine (Fe-CD). Fe(III) in Fe-CD reacted with GSH by redox reactions and consumed it, which recovered the strong fluorescence of CD to realize fluorescence imaging of the process of GSH depletion.

CRediT authorship contribution statement

Jun Li: Investigation, Writing – review & editing. Zu-E Hu: Investigation, Writing – review & editing. Yun-Jie We: Investigation, Formal analysis. Yan-Hong Liu: Formal analysis, Validation. Na Wang: Conceptualization, Supervision, Funding acquisition. Xiao-Qi Yu: Conceptualization, Supervision, Funding acquisition.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgements

This project was supported by the National Natural Science Foundation of China (No: 21877082) and the National Key R&D Program of China (Grant No. 2018YFA0901600). We also acknowledge the Comprehensive Training Platform of Specialized Laboratory, College of Chemistry, Sichuan University. We also appreciate Shuguang Yan from the Analytical & Testing Center of Sichuan University for providing help with XPS characterization.

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Multifunctional carbon quantum dots as a theranostic nanomedicine for fluorescence imaging-guided glutathione depletion to improve chemodynamic therapy

Abstract

Graphical abstract

Section snippets

1. Introduction

Materials and methods

Synthesis of Fe-CD

Conclusions

CRediT authorship contribution statement

Declaration of Competing Interest

Acknowledgements

Cell Metab.

J Colloid Interface Sci

Int. J. Biochem. Cell Biol.

Free Radic. Biol. Med.

Biomaterials

Biomaterials

J. Colloid Interface Sci.

Chem. Eng. J.

J. Photochem. Photobiol. A

Mater. Today Chem.

Mater. Sci. Eng. C

Mater. Sci. Eng. C

Sens. Actuator B-Chem.

Biosens. Bioelectron.

Anal. Chim. Acta

Carbon

Biomaterials

Fundamentals of cancer metabolism

Sci. Adv.

Modifying the tumor microenvironment using nanoparticle therapeutics, Wiley Interdiscip

Rev.-Nanomed. Nanobiotechnol.

Synthesis of Iron Nanometallic Glasses and Their Application in Cancer Therapy by a Localized Fenton Reaction

Angew. Chem.-Int. Edit.

Chemodynamic Therapy: Tumour Microenvironment-Mediated Fenton and Fenton-like Reactions

Angew. Chem.-Int. Edit.

Recent Advances in Nanomaterial-Based Nanoplatforms for Chemodynamic Cancer Therapy

Adv. Funct. Mater.

Nanoparticle-triggered in situ catalytic chemical reactions for tumour-specific therapy

Chem. Soc. Rev.

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Chem. Rev.