Manganese dioxide nanosheets: from preparation to biomedical applications

Abstract

Advancements in nanotechnology and molecular biology have promoted the development of a diverse range of models to intervene in various disorders (from diagnosis to treatment and even theranostics). Manganese dioxide nanosheets (MnO₂ NSs), a typical two-dimensional (2D) transition metal oxide of nanomaterial that possesses unique structure and distinct properties have been employed in multiple disciplines in recent decades, especially in the field of biomedicine, including biocatalysis, fluorescence sensing, magnetic resonance imaging and cargo-loading functionality. A brief overview of the different synthetic methodologies for MnO₂ NSs and their state-of-the-art biomedical applications is presented below, as well as the challenges and future perspectives of MnO₂ NSs.

Keywords: MnO2 nanosheets; biocatalysis; controlled drug delivery; fluorescence sensing; stimuli-activated imaging; synthetic methods.

Figure 1

Schematic illustration of the single-step oxidative method with H₂O₂ at room temperature versus the conventional method. Note: Reprinted with permission from Kai K, Yoshida Y, Kageyama H, et al. Room-temperature synthesis of manganese oxide monosheets. J Am Chem Soc. 2008;130(47):15938–15943. Copyright (2008) American Chemical Society.

Figure 2

(A) Schematic illustration for the control experiments of reductants employed in the growth of MnO₂ nanomaterials at ambient temperature (left) and TEM characterization of the corresponding products (right). Reprinted with permission from Deng R, Xie X, Vendrell M, Chang Y, Liu X. Intracellular glutathione detection using MnO(2)-nanosheet-modified upconversion nanoparticles. J Am Chem Soc. 2011;133(50):20168–20171. Copyright 2011 American Chemical Society. (B) Schematic illustration for MnO₂ NS formation based on the KMnO₄ and SDS reaction. Reprinted with permission fromLiu Z, Xu K, Sun H, Yin S. One-step synthesis of single-layer MnO2 nanosheets with multi-role sodium dodecyl sulfate for highperformance pseudocapacitors. Small. 2015;11(18):2182–2191. Copyright © 2015, John Wiley and Sons.

Figure 3

Schematic illustration of the diverse roles MnO₂ NSs have played in the field of biomedicine.

Figure 4

(A) Illustration of the MnO₂ NS-based colorimetric assay for GSH quantification, where the MnO₂ NSs acted as an oxidase-like nanozyme for the formation of ox-TMB and GSSG. Reprinted from Biosensors and Bioelectronics, 90, Liu J, Meng L, Fei Z, Dyson P, Jing X, Liu X. MnO nanosheets as an artificial enzyme to mimic oxidase for rapid and sensitive detection of glutathione, 69–74, Copyright (2017), with permission from Elsevier. (B) Schematic design of the Janus protected DNA nanomachine, where miRNA-21 is employed as a model cellular RNA target (green sequence), the red X denotes DNA, PS (phosphorothioate)-DNA, 2ʹOMe (methylation)-DNA and LNA (locked nuclease acid) monomers, which are highlighted in the DNA partzymes (gray sequences). Reprinted with permission from Chen F, Bai M, Zhao Y, Cao K, Cao X, Zhao Y. MnO-nanosheet-powered protective janus DNA nanomachines supporting robust RNA imaging. Anal Chem. 2018;90(3):2271–2276. Copyright 2018 American Chemical Society.

Figure 5

(A) Schematic illustration of the preparation of CDs-MnO₂ NSs and the principle of the FRET-based CD-MnO₂ NSs architecture for GSH sensing. Republished with permission of Royal Society of Chemistry, from A sensitive turn-on fluorescent probe for intracellular imaging of glutathione using single-layer MnO2 nanosheet-quenched fluorescent carbon quantum dots, He D, Yang X, He X, et al, 51, 79, 2015; permission conveyed through Copyright Clearence Centre, Inc. (B) Scheme for the preparation of MnO₂ NSs and the mechanism of a GQD-MnO₂ NS-based optical sensing nanoplatform for monitoring GSH in MCF-7 cells. Reprinted with permission from Yan X, Song Y, Zhu C, et al. Graphene quantum dot-MnO2 nanosheet based optical sensing platform: a sensitive fluorescence“Turn Off-On” nanosensor for glutathione detection and intracellular imaging. ACS Appl Mater Interfaces. 2016;8(34):21990–21996. Copyright 2016 American Chemical Society. (C) Schematic illustration of a g-C₃N₄ NS-MnO₂ NS sandwich-like nanocomposite for GSH sensing. Reprinted with permission from Zhang X, Zheng C, Guo S, Li J, Yang H, Chen G. Turn-on fluorescence sensor for intracellular imaging of glutathione using g-C3N4 nanosheet-MnO2 sandwich nanocomposite. Anal Chem. 2014;86(7):3426–3434. Copyright 2014 American Chemical Society.

Figure 6

Schematic illustration of the MnO₂ NS-mediated intracellular-hybridized chain reaction (HCR) signal amplification system for efficiently detecting miRNA-21 in living HeLa cells. The MnO₂ NSs could deliver two types of hairpin DNA probes into the cytosol. Overexpressed glutathione (GSH) in HeLa cells and displacement reactions by other proteins or nucleic acids promoted the decomposition of the MnO₂ NSs to release free hairpins, which assembled into double-stranded (dsDNA) polymers upon binding to the target miRNA-21. Subsequently, enhanced FRET signals were produced to realize accurate and sensitive detection. Reprinted with permission from Li J, Li D, Yuan R, Xiang Y. Biodegradable MnO2 nanosheet-mediated signal amplification in living cells enables sensitive detection of down-regulated intracellular MicroRNA. ACS Appl Mater Interfaces. 2017;9(7):5717–5724. Copyright 2017 American Chemical Society.

Figure 7

(A) Schematic illustration of the synthetic procedure for the preparation of the MSU/MnO₂-CR drug delivery system. (B) Images of the MSU/MnO₂-CR system before and after drug delivery under 980 nm excitation. Republished with permission of Royal Society of Chemistry, from Multifunctional MnO2 nanosheet-modified Fe3O4@SiO2/NaYF4: yb,Er nanocomposites as novel drug carriers, Zhao P, Zhu Y, Yang X, et al, 43, 2, 2014; permission conveyed through Copyright Clearence Centre, Inc.

Figure 8

(A) Determination of the T₁ (left) and T₂ (right) relaxation rates of a MnO₂ nanosheet solution (red lines) and MnO₂ nanosheet solution treated with GSH (black lines). The related T₁-weighted and T₂-weighted MRI images were presented below. (B) Schematic illustration of the activation mechanism of the MnO₂ NS-aptamer nanoprobe for fluorescence/MRI bimodal tumor cell imaging. Reprinted with permission from Zhao Z, Fan H, Zhou G, et al. Activatable fluorescence/MRI bimodal platform for tumor cell imaging via MnO2 nanosheet-aptamer nanoprobe. J Am Chem Soc. 2014;136(32):11220–11223. Copyright 2014 American Chemical Society.

Figure 9

(A) Schematic illustration of the synthetic procedure for the PEG-MnO₂ NSs. (B) Theranostic functionality of the PEG-MnO₂ NSs for intracellular pH-responsive drug release and the axial and coronal T₁-MRI images of 4T1 tumor-bearing nude mice before (a₁, b₁) and after (a₂ – a₉ and b₂ – b₉) administration of the PEG–MnO₂ nanosheets within the tumor and normal subcutaneous tissue. PEG denotes ethylene glycol. Reproduced with permission from Chen Y, Ye D, Wu M, et al. Break-up of two-dimensional MnO2 nanosheets promotes ultrasensitive pH-triggered theranostics of cancer. Adv Mater Weinheim. 2014;26(41):7019–7026. Copyright © 2014, John Wiley and Sons.

Figure 10

Schematic illustrations of the mechanism and application of mesoporous silicon (MS)@MnO₂ NPs for MRI-monitored chemo-chemodynamic combination therapy. Reproduced with permission from Lin L, Song J, Song L, et al. Simultaneous fenton-like ion delivery and glutathione depletion by MnO-based nanoagent to enhance chemodynamic therapy. Angew Chem Int Ed Engl. 2018;57(18):4902–4906. Copyright © 2018, John Wiley and Sons.