Skip to main content
SpringerLink
Log in

Mechanism underlying the effect of MnO2 nanosheets for A549 cell chemodynamic therapy

  • Original Paper
  • Published:
Microchimica Acta Aims and scope Submit manuscript

Abstract  

MnO2 nanosheets (MnO2NSs) were synthesized by one-step method, and MnO2NSs were applied to A549 cell chemodynamic Therapy (CDT). The cytotoxicity, redox ability, and reactive oxygen species production of MnO2NSs have been investigated, and differences in cell metabolism during CDT were determined using liquid chromatography-mass spectrometry (LC–MS/MS). In addition, the metabolites of A549 lung cancer cells affected by MnO2NSs treatment are identified; metabolite differences were identified by PCA, PLS-DA, orthogonal PLS-DA, and other methods; and these differences were analyzed using non-targeted metabolomics. We found that A549 cells which were treated by MnO2NSs have 17 different metabolites and 9 metabolic pathways that varied markedly. Owing to their unique composition, structure, and physicochemical properties, MnO2NSs and their composites have become a favored type of nanomaterial used for CDT in cancer therapy. This work provides insights into the mechanism underlying the effects of MnO2NSs on the tumor microenvironment of A549 lung cancer cells, effectively making up for the deficiency of the study on cellular mechanism of CDT-induced apoptosis of cancer cells. It could aid the development of cancer CDT treatment strategies and help improve the use of nanomaterials in the clinical field.

Graphical Abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Scheme 1
Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12

Similar content being viewed by others

Data availability

Not applicable.

References

  1. Qu X, Zhou D, Lu J, Qin D, Zhou J, Liu H-J (2023) Cancer nanomedicine in preoperative therapeutics: nanotechnology-enabled neoadjuvant chemotherapy, radiotherapy, immunotherapy, and phototherapy. Bioact Mater 24:136–152. https://doi.org/10.1016/j.bioactmat.2022.12.010

    Article  CAS  PubMed  Google Scholar 

  2. Karges J (2022) Clinical development of metal complexes as photosensitizers for photodynamic therapy of cancer. Angew Chem Int Ed 61:e202112236. https://doi.org/10.1002/anie.202112236

    Article  CAS  Google Scholar 

  3. Li Y, Yang J, Gu G, Guo X, He C, Sun J, Zou H, Wang H, Liu S, Li X, Zhang S, Wang K, Yang L, Jiang Y, Wu L, Sun X (2022) Pulmonary delivery of theranostic nanoclusters for lung cancer ferroptosis with enhanced chemodynamic/radiation synergistic therapy. Nano Lett 22:963–972. https://doi.org/10.1021/acs.nanolett.1c03786

    Article  CAS  PubMed  Google Scholar 

  4. Pasello G, Scattolin D, Bonanno L, Caumo F, Dell’Amore A, Scagliori E, Tinè M, Calabrese F, Benati G, Sepulcri M, Baiocchi C, Milella M, Rea F, Guarneri V (2023) Secondary prevention and treatment innovation of early stage non-small cell lung cancer: impact on diagnostic-therapeutic pathway from a multidisciplinary perspective. Cancer Treat Rev 116:102544. https://doi.org/10.1016/j.ctrv.2023.102544

    Article  PubMed  Google Scholar 

  5. Liu S, Wei W, Wang J, Chen T (2023) Theranostic applications of selenium nanomedicines against lung cancer. J Nanobiotechnol 21:96. https://doi.org/10.1186/s12951-023-01825-2

    Article  CAS  Google Scholar 

  6. Zhou Z, Du C, Zhang Q, Yu G, Zhang F, Chen X (2021) Exquisite vesicular nanomedicine by paclitaxel mediated co-assembly with camptothecin prodrug. Angew Chem Int Ed 60:21033–21039. https://doi.org/10.1002/anie.202108658

    Article  CAS  Google Scholar 

  7. Huang R, Zhang C, Bu Y, Li Z, Zheng X, Qiu S, Machuki JOA, Zhang L, Yang Y, Guo K, Gao F (2021) A multifunctional nano-therapeutic platform based on octahedral yolk-shell Au NR@CuS: Photothermal/photodynamic and targeted drug delivery tri-combined therapy for rheumatoid arthritis. Biomaterials 277:121088. https://doi.org/10.1016/j.biomaterials.2021.121088

    Article  CAS  PubMed  Google Scholar 

  8. Li C, Gao Y, Wang Y, Wang J, Lin J, Du J, Zhou Z, Liu X, Yang S, Yang H (2023) Bifunctional nano-assembly of iridium(III) phthalocyanine complex encapsulated with BSA: hypoxia-relieving/sonosensitizing effects and their immunogenic sonodynamic therapy. Adv Funct Mater 33:2210348. https://doi.org/10.1002/adfm.202210348

    Article  CAS  Google Scholar 

  9. Liang G, Sadhukhan T, Banerjee S, Tang D, Zhang H, Cui M, Montesdeoca N, Karges J, Xiao H (2023) Reduction of platinum(IV) prodrug hemoglobin nanoparticles with deeply-penetrating ultrasound radiation for tumor-targeted therapeutically enhanced anticancer therapy. Angew Chem Int Ed 62:e202301074. https://doi.org/10.1002/anie.202301074

    Article  CAS  Google Scholar 

  10. Tang Z, Zhao P, Wang H, Liu Y, Bu W (2021) Biomedicine meets Fenton chemistry. Chem Rev 121:1981–2019. https://doi.org/10.1021/acs.chemrev.0c00977

    Article  CAS  PubMed  Google Scholar 

  11. Tang Z, Liu Y, He M, Bu W (2019) Chemodynamic therapy: tumour microenvironment-mediated Fenton and Fenton-like reactions. Angew Chem Int Ed 58:946–956. https://doi.org/10.1002/anie.201805664

    Article  CAS  Google Scholar 

  12. Xu X, Zeng Z, Chen J, Huang B, Guan Z, Huang Y, Huang Z, Zhao C (2020) Tumor-targeted supramolecular catalytic nanoreactor for synergistic chemo/chemodynamic therapy via oxidative stress amplification and cascaded Fenton reaction. Chem Eng J 390:124628. https://doi.org/10.1016/j.cej.2020.124628

    Article  CAS  Google Scholar 

  13. Tang Z, Zhang H, Liu Y, Ni D, Zhang H, Zhang J, Yao Z, He M, Shi J, Bu W (2017) Antiferromagnetic pyrite as the tumor microenvironment-mediated nanoplatform for self-enhanced tumor imaging and therapy. Adv Mater 29:1701683. https://doi.org/10.1002/adma.201701683

    Article  CAS  Google Scholar 

  14. Ranji-Burachaloo H, Gurr PA, Dunstan DE, Qiao GG (2018) Cancer treatment through nanoparticle-facilitated Fenton reaction. ACS Nano 12:11819–11837. https://doi.org/10.1021/acsnano.8b07635

    Article  CAS  PubMed  Google Scholar 

  15. Ma B, Wang S, Liu F, Zhang S, Duan J, Li Z, Kong Y, Sang Y, Liu H, Bu W, Li L (2019) Self-assembled copper–amino acid nanoparticles for in situ glutathione “and” H2O2 sequentially triggered chemodynamic therapy. J Am Chem Soc 141:849–857. https://doi.org/10.1021/jacs.8b08714

    Article  CAS  PubMed  Google Scholar 

  16. Xiao J, Zhang G, Xu R, Chen H, Wang H, Tian G, Wang B, Yang C, Bai G, Zhang Z, Yang H, Zhong K, Zou D, Wu Z (2019) A pH-responsive platform combining chemodynamic therapy with limotherapy for simultaneous bioimaging and synergistic cancer therapy. Biomaterials 216:119254. https://doi.org/10.1016/j.biomaterials.2019.119254

    Article  CAS  PubMed  Google Scholar 

  17. Zhang C, Bu W, Ni D, Zhang S, Li Q, Yao Z, Zhang J, Yao H, Wang Z, Shi J (2016) Synthesis of iron nanometallic glasses and their application in cancer therapy by a localized Fenton reaction. Angew Chem Int Ed 55:2101–2106. https://doi.org/10.1002/anie.201510031

    Article  CAS  Google Scholar 

  18. Dong Z, Feng L, Chao Y, Hao Y, Chen M, Gong F, Han X, Zhang R, Cheng L, Liu Z (2019) Amplification of tumor oxidative stresses with liposomal Fenton catalyst and glutathione inhibitor for enhanced cancer chemotherapy and radiotherapy. Nano Lett 19:805–815. https://doi.org/10.1021/acs.nanolett.8b03905

    Article  CAS  PubMed  Google Scholar 

  19. Noh J, Kwon B, Han E, Park M, Yang W, Cho W, Yoo W, Khang G, Lee D (2015) Amplification of oxidative stress by a dual stimuli-responsive hybrid drug enhances cancer cell death. Nat Commun 6:6907. https://doi.org/10.1038/ncomms7907

    Article  CAS  PubMed  Google Scholar 

  20. Fan W, Huang P, Chen X (2016) Overcoming the Achilles’ heel of photodynamic therapy. Chem Soc Rev 45:6488–6519. https://doi.org/10.1039/C6CS00616G

    Article  CAS  PubMed  Google Scholar 

  21. Schumacker PT (2006) Reactive oxygen species in cancer cells: Live by the sword, die by the sword. Cancer Cell 10:175–176. https://doi.org/10.1016/j.ccr.2006.08.015

    Article  CAS  PubMed  Google Scholar 

  22. Cao S, Li X, Gao Y, Li F, Li K, Cao X, Dai Y, Mao L, Wang S, Tai X (2020) A simultaneously GSH-depleted bimetallic Cu(ii) complex for enhanced chemodynamic cancer therapy. Dalton T 49:11851–11858. https://doi.org/10.1039/D0DT01742F

    Article  CAS  Google Scholar 

  23. Aioub M, Panikkanvalappil SR, El-Sayed MA (2017) Platinum-Coated Gold Nanorods: Efficient Reactive Oxygen Scavengers That Prevent Oxidative Damage toward Healthy, Untreated Cells during Plasmonic Photothermal Therapy. ACS Nano 11:579–586. https://doi.org/10.1021/acsnano.6b06651

    Article  CAS  PubMed  Google Scholar 

  24. Yu X-a, Lu M, Luo Y, Hu Y, Zhang Y, Xu Z, Gong S, Wu Y, Ma X-N, Yu B-Y, Tian J (2020) A cancer-specific activatable theranostic nanodrug for enhanced therapeutic efficacy via amplification of oxidative stress. Theranostics 10:371–383. https://doi.org/10.7150/thno.39412

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Zong Q, Wang K, Xiao X, Jiang M, Li J, Yuan Y, Wang J (2021) Amplification of tumor oxidative stresses by Poly(disulfide acetal) for multidrug resistance reversal. Biomaterials 276:121005. https://doi.org/10.1016/j.biomaterials.2021.121005

    Article  CAS  PubMed  Google Scholar 

  26. Hou L, Gong F, Han Z, Wang Y, Yang Y, Cheng S, Yang N, Liu Z, Cheng L (2022) HXV2O5 nanocatalysts combined with ultrasound for triple amplification of oxidative stress to enhance cancer catalytic therapy. Angew Chem Int Ed 61:e202208849. https://doi.org/10.1002/anie.202208849

    Article  CAS  Google Scholar 

  27. Cui XY, Park SH, Park WH (2022) Anti-cancer effects of auranofin in human lung cancer cells by increasing intracellular ROS levels and depleting GSH levels. Molecules 27:5207. https://doi.org/10.3390/molecules27165207

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Yang G, Xu L, Chao Y, Xu J, Sun X, Wu Y, Peng R, Liu Z (2017) Hollow MnO2 as a tumor-microenvironment-responsive biodegradable nano-platform for combination therapy favoring antitumor immune responses. Nat Commun 8:902. https://doi.org/10.1038/s41467-017-01050-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Lin L-S, Song J, Song L, Ke K, Liu Y, Zhou Z, Shen Z, Li J, Yang Z, Tang W, Niu G, Yang H-H, Chen X (2018) Simultaneous Fenton-like Ion delivery and glutathione depletion by mno2-based nanoagent to enhance chemodynamic therapy. Angew Chem Int Ed 57:4902–4906. https://doi.org/10.1002/anie.201712027

    Article  CAS  Google Scholar 

  30. Hu X, Zhang L, Wang W, Zhang Y, Wang J (2023) Mitochondria-targeted and multistage synergistic ROS-elevated drug delivery system based on surface decorated MnO2 with CeO2 for enhanced chemodynamic/chemotherapy. Colloids Surf A Physicochem Eng Asp 656:130495. https://doi.org/10.1016/j.colsurfa.2022.130495

    Article  CAS  Google Scholar 

  31. Wang S, Pang Y, Hu S, Lv J, Lin Y, Li M (2023) Copper sulfide engineered covalent organic frameworks for pH-responsive chemo/photothermal/chemodynamic synergistic therapy against cancer. Chem Eng J 451:138864. https://doi.org/10.1016/j.cej.2022.138864

    Article  CAS  Google Scholar 

  32. Wang C, Cao F, Ruan Y, Jia X, Zhen W, Jiang X (2019) Specific generation of singlet oxygen through the russell mechanism in hypoxic tumors and GSH depletion by Cu-TCPP nanosheets for cancer therapy. Angew Chem Int Ed 58:9846–9850. https://doi.org/10.1002/anie.201903981

    Article  CAS  Google Scholar 

  33. Wen C, Guo X, Gao C, Zhu Z, Meng N, Shen X-C, Liang H (2022) NIR-II-responsive AuNRs@SiO2–RB@MnO2 nanotheranostic for multimodal imaging-guided CDT/PTT synergistic cancer therapy. J Mater Chem B 10:4274–4284. https://doi.org/10.1039/D1TB02807C

    Article  CAS  PubMed  Google Scholar 

  34. Wang H, Bremner DH, Wu K, Gong X, Fan Q, Xie X, Zhang H, Wu J, Zhu L-M (2020) Platelet membrane biomimetic bufalin-loaded hollow MnO2 nanoparticles for MRI-guided chemo-chemodynamic combined therapy of cancer. Chem Eng J 382:122848. https://doi.org/10.1016/j.cej.2019.122848

    Article  CAS  Google Scholar 

  35. Zhu S, Han X, Yang R, Tian Y, Zhang Q, Wu Y, Dong S, Zhang B (2023) Metabolomics study of ribavirin in the treatment of orthotopic lung cancer based on UPLC-Q-TOF/MS. Chem Biol Interact 370:110305. https://doi.org/10.1016/j.cbi.2022.110305

    Article  CAS  PubMed  Google Scholar 

  36. Chen X, Sun M, Yang Z (2022) Single cell mass spectrometry analysis of drug-resistant cancer cells: metabolomics studies of synergetic effect of combinational treatment. Anal Chim Acta 1201:339621. https://doi.org/10.1016/j.aca.2022.339621

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Li X, Hu H, Yin R, Li Y, Sun X, Dey SK, Laskin J (2022) high-throughput nano-DESI mass spectrometry imaging of biological tissues using an integrated microfluidic probe. Anal Chem 94:9690–9696. https://doi.org/10.1021/acs.analchem.2c01093

    Article  CAS  PubMed  Google Scholar 

  38. Tan Q, Zhang R, Kong R, Kong W, Zhao W, Qu F (2017) Detection of glutathione based on MnO2 nanosheet-gated mesoporous silica nanoparticles and target induced release of glucose measured with a portable glucose meter. Microchim Acta 185:44. https://doi.org/10.1007/s00604-017-2603-7

    Article  CAS  Google Scholar 

  39. Kai K, Yoshida Y, Kageyama H, Saito G, Ishigaki T, Furukawa Y, Kawamata J (2008) Room-temperature synthesis of manganese oxide monosheets. J Am Chem Soc 130:15938–15943. https://doi.org/10.1021/ja804503f

    Article  CAS  PubMed  Google Scholar 

  40. Lu Z, Liu S, Le Y, Qin Z, He M, Xu F, Zhu Y, Zhao J, Mao C, Zheng L (2019) An injectable collagen-genipin-carbon dot hydrogel combined with photodynamic therapy to enhance chondrogenesis. Biomaterials 218:119190. https://doi.org/10.1016/j.biomaterials.2019.05.001

    Article  CAS  PubMed  Google Scholar 

  41. Haidar LL, Baldry M, Fraser ST, Boumelhem BB, Gilmour AD, Liu Z, Zheng Z, Bilek MMM, Akhavan B (2022) Surface-active plasma-polymerized nanoparticles for multifunctional diagnostic, targeting, and therapeutic probes. ACS Appl Nano Mater 5:17576–17591. https://doi.org/10.1021/acsanm.2c03213

    Article  CAS  Google Scholar 

  42. Zhang J, Shi J, Han S, Zheng P, Chen Z, Jia G (2022) Titanium dioxide nanoparticles induced reactive oxygen species (ROS) related changes of metabolomics signatures in human normal bronchial epithelial (BEAS-2B) cells. Toxicol Appl Pharmacol 444:116020. https://doi.org/10.1016/j.taap.2022.116020

    Article  CAS  PubMed  Google Scholar 

  43. Lin X-C, Chen F, Zhang K, Li J, Jiang J-H, Yu R-Q (2022) Single molecule-level detection via liposome-based signal amplification mass spectrometry counting assay. Anal Chem 94:6120–6129. https://doi.org/10.1021/acs.analchem.1c04984

    Article  CAS  PubMed  Google Scholar 

  44. Worley B, Powers R (2016) PCA as a practical indicator of OPLS-DA model reliability. Curr Metabolomics 4:97–103. https://doi.org/10.2174/2213235X04666160613122429

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Yuan H, Liu C, Wang H, Wang L, Dai L (2022) PLS-DA and Vis-NIR spectroscopy based discrimination of abdominal tissues of female rabbits. Spectrochim Acta Part A Mol Biomol Spectrosc 271:120887. https://doi.org/10.1016/j.saa.2022.120887

    Article  CAS  Google Scholar 

  46. Kang C, Zhang Y, Zhang M, Qi J, Zhao W, Gu J, Guo W, Li Y (2022) Screening of specific quantitative peptides of beef by LC–MS/MS coupled with OPLS-DA. Food Chem 387:132932. https://doi.org/10.1016/j.foodchem.2022.132932

    Article  CAS  PubMed  Google Scholar 

  47. Tang W, Fan W, Zhang W, Yang Z, Li L, Wang Z, Chiang YL, Liu Y, Deng L, He L, Shen Z, Jacobson O, Aronova MA, Jin A, Xie J, Chen X (2019) Wet/Sono-Chemical Synthesis of Enzymatic Two-Dimensional MnO(2) Nanosheets for Synergistic Catalysis-Enhanced Phototheranostics. Adv Mater 31:e1900401. https://doi.org/10.1002/adma.201900401

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Zhu D, Zhu X-H, Ren S-Z, Lu Y-D, Zhu H-L (2021) Manganese dioxide (MnO2) based nanomaterials for cancer therapies and theranostics. J Drug Target 29:911–924. https://doi.org/10.1080/1061186x.2020.1815209

    Article  CAS  PubMed  Google Scholar 

  49. Guangbao Y, Jiansong J, Zhuang L (2021) Multifunctional MnO2 nanoparticles for tumor microenvironment modulation and cancer therapy. WIREs Nanomed Nanobiotechnol 13:1720. https://doi.org/10.1002/wnan.1720

    Article  CAS  Google Scholar 

  50. Ogretmen B (2018) Sphingolipid metabolism in cancer signalling and therapy. Nat Rev Cancer 18:33–50. https://doi.org/10.1038/nrc.2017.96

    Article  CAS  PubMed  Google Scholar 

  51. Lin M, Li Y, Wang S, Cao B, Li C, Li G (2022) Sphingolipid metabolism and signaling in lung cancer: a potential therapeutic target. J Oncol 2022:9099612. https://doi.org/10.1155/2022/9099612

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This work is financially supported by National Natural Science Foundation of China (21864009, 22064018), Natural Science Foundation of Guangxi Zhuang Autonomous Region (2018GXNSFAA281197), Bagui Scholars Program of Guangxi Zhuang Autonomous Region, and Guangxi Collaborative Innovation Centre of Structure and Property for New Energy and Materials.

Author information

Authors and Affiliations

  1. Guangxi Key Laboratory of Information Materials, School of Materials Science and Engineering, Guilin University of Electronic Technology, Guilin, 541004, China

    Jian Liu, Miaomiao Hu & Xiang-Cheng Lin

  2. State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmacy Sciences, Guangxi Normal University, Guilin, 541004, China

    Changchun Wen & Nan Leng

Authors
  1. Jian Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Changchun Wen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Miaomiao Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nan Leng
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xiang-Cheng Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conceptualization – J. Liu, C. Wen, X-C. Lin; original draft writing – J. Liu, C. Wen, X-C. Lin; illustrations – J. Liu, M. Hu; proofreading – N. Leng, C. Wen, X-C. Lin; all authors read and approved the final manuscript.

Corresponding authors

Correspondence to Changchun Wen or Xiang-Cheng Lin.

Ethics declarations

Ethical approval

Not applicable.

Competing interests

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (1.57 MB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liu, J., Wen, C., Hu, M. et al. Mechanism underlying the effect of MnO2 nanosheets for A549 cell chemodynamic therapy. Microchim Acta 190, 381 (2023). https://doi.org/10.1007/s00604-023-05974-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s00604-023-05974-x

Keywords

Search

Navigation