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Hollow mesoporous MnO2-carbon nanodot-based nanoplatform for GSH depletion enhanced chemodynamic therapy, chemotherapy, and normal/cancer cell differentiation

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Abstract

A redox-responsive chemodynamic therapy (CDT)-based theranostic system composed of hollow mesoporous MnO2 (H-MnO2), doxorubicin (DOX), and fluorescent (FL) carbon nanodots (CDs) is reported for the diagnosis and therapy of cancer. In general, since H-MnO2 can be degraded by intracellular glutathione (GSH) to form Mn2+ with excellent Fenton-like activity to generate highly reactive ·OH, the normal antioxidant defense system can be injured via consumption of GSH. This in turn can potentiate the cytotoxicity of CDT and release DOX. The cancer cells can be eliminated effectively by the nanoplatform via the synergistic effect of chemotherapy and CDT. The FL of CDs can be restored after H-MnO2 is degraded which blocked the fluorescence resonance energy transfer process between CDs as an energy donor and H-MnO2 as an FL acceptor. The GSH can be determined by recovery of the FL and limit of detection is 1.30 μM with a linear range of 0.075–0.825 mM. This feature can be utilized to efficiently distinguish cancerous cells from normal ones based on different GSH concentrations in the two types of cells. As a kind of CDT-based theranostic system responsive to GSH, simultaneously diagnostic (normal/cancer cell differentiation) and therapeutic function (chemotherapy and CDT) in a single nanoplatform can be achieved.

Graphical abstract

The redox-responsive chemodynamic therapy (CDT)-based theranostic system is fabricated by H-MnO2, DOX, and fluorescent CDs. The nanoplatform can realize simultaneously diagnostic (normal/cancer cell differentiation) and therapeutic function (chemotherapy and CDT) to improve the therapeutic efficiency and security.

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References

  1. Zhang Y, Bo S, Feng T, Qin X, Wan Y, Jiang S, Li C, Lin J, Wang T, Zhou X, Jiang Z-X, Huang P (2019) A versatile theranostic nanoemulsion for architecture-dependent multimodal imaging and dually augmented photodynamic therapy. Adv Mater 31(21):1806444

    Article  Google Scholar 

  2. Kim H, Kwak G, Kim K, Yoon HY, Kwon IC (2019) Theranostic designs of biomaterials for precision medicine in cancer therapy. Biomaterials 213:119207

    Article  CAS  Google Scholar 

  3. Lim EK, Kim T, Paik S, Haam S, Huh YM, Lee K (2015) Nanomaterials for theranostics: recent advances and future challenges. Chem Rev 115(1):327–394

    Article  CAS  Google Scholar 

  4. Xie J, Liu G, Eden HS, Ai H, Chen X (2011) Surface-engineered magnetic nanoparticle platforms for cancer imaging and therapy. Acc Chem Res 44(10):883–892

    Article  CAS  Google Scholar 

  5. Zheng M, Liu S, Li J, Qu D, Zhao H, Guan X, Hu X, Xie Z, Jing X, Sun Z (2014) Integrating oxaliplatin with highly luminescent carbon dots: an unprecedented theranostic agent for personalized medicine. Adv Mater 26(21):3554–3560

    Article  CAS  Google Scholar 

  6. Tang Z, Liu Y, He M, Bu W (2019) Chemodynamic therapy: tumour microenvironment-mediated Fenton and Fenton-like reactions. Angew Chem Int Ed 58(4):946–956

    Article  CAS  Google Scholar 

  7. Li X, Lee D, Huang J-D, Yoon J (2018) Phthalocyanine-assembled nanodots as photosensitizers for highly efficient type I photoreactions in photodynamic therapy. Angew Chem Int Ed 57(31):9885–9890

    Article  CAS  Google Scholar 

  8. McHale A P, Callan J F, Nomikou N, Fowley C, Callan B (2016) Sonodynamic therapy: concept, mechanism and application to cancer treatment. In: Therapeutic Ultrasound. Springer, pp. 429–450

  9. Kumar R, Shin WS, Sunwoo K, Kim WY, Koo S, Bhuniya S, Kim JS (2015) Small conjugate-based theranostic agents: an encouraging approach for cancer therapy. Chem Soc Rev 44(19):6670–6683

    Article  CAS  Google Scholar 

  10. Kosaka PM, Pini V, Ruz JJ, Da Silva R, González M, Ramos D, Calleja M, Tamayo J (2014) Detection of cancer biomarkers in serum using a hybrid mechanical and optoplasmonic nanosensor. Nat Nanotechnol 9(12):1047–1053

    Article  CAS  Google Scholar 

  11. Savla R, Taratula O, Garbuzenko O, Minko T (2011) Tumor targeted quantum dot-mucin 1 aptamer-doxorubicin conjugate for imaging and treatment of cancer. J Control Release 153(1):16–22

    Article  CAS  Google Scholar 

  12. Schnelldorfer T, Gansauge S, Gansauge F, Schlosser S, Beger HG, Nussler AK (2000) Glutathione depletion causes cell growth inhibition and enhanced apoptosis in pancreatic cancer cells. Cancer 89(7):1440–1447

    Article  CAS  Google Scholar 

  13. Xu J, Han W, Yang P, Jia T, Dong S, Bi H, Gulzar A, Yang D, Gai S, He F (2018) Tumor microenvironment-responsive mesoporous MnO2-coated upconversion nanoplatform for self-enhanced tumor theranostics. Adv Funct Mater 28(36):1803804

    Article  Google Scholar 

  14. Yan X, Song Y, Zhu C, Song J, Du D, Su X, Lin Y (2016) 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 8(34):21990–21996

    Article  CAS  Google Scholar 

  15. 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(18):4902–4906

    Article  CAS  Google Scholar 

  16. Xu Z, Liu Y (2021) The behavior of carbonized polymer dots at the nano-bio interface and their luminescent mechanism: a physical chemistry perspective. Chin J Chem 39:265–273

    Article  CAS  Google Scholar 

  17. Huang Q, Lin X, Li F, Weng W, Lin L, Hu S (2015) Synthesis and applications of carbon dots. Prog Chem 27(11):1604–1614

    CAS  Google Scholar 

  18. Sohal N, Maity B, Basu S (2020) Carbon dot─MnO2 nanosphere composite sensors for selective detection of glutathione. ACS Appl Nano Mater 3(6):5955–5964

    Article  CAS  Google Scholar 

  19. Cai Q-Y, Li J, Ge J, Zhang L, Hu Y-L, Li Z-H, Qu L-B (2015) A rapid fluorescence “switch-on” assay for glutathione detection by using carbon dots–MnO2 nanocomposites. Biosens Bioelectron 72:31–36

    Article  CAS  Google Scholar 

  20. Yang C, Deng W, Liu H, Ge S, Yan M (2015) Turn-on fluorescence sensor for glutathione in aqueous solutions using carbon dots─MnO2 nanocomposites. Sensor Actuat B 216:286–292

    Article  CAS  Google Scholar 

  21. 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(1):902

    Article  Google Scholar 

  22. Zhu S, Meng Q, Wang L, Zhang J, Song Y, Jin H, Zhang K, Sun H, Wang H, Yang B (2013) Highly photoluminescent carbon dots for multicolor patterning, sensors, and bioimaging. Angew Chem Int Ed 52(14):3953–3957

    Article  CAS  Google Scholar 

  23. Xu Z-Q, Lan J-Y, Jin J-C, Dong P, Jiang F-L, Liu Y (2015) Highly photoluminescent nitrogen-doped carbon nanodots and their protective effects against oxidative stress on cells. ACS Appl Mater Interfaces 7(51):28346–28352

    Article  CAS  Google Scholar 

  24. Niu Z, Yue T, Hu W, Sun W, Hu Y, Xu Z (2019) Covalent bonding of MnO2 onto graphene aerogel forwards: efficiently catalytic degradation of organic wastewater. Appl Surf Sci 496:143585

    Article  CAS  Google Scholar 

  25. Wang K, Liu Y, Yi W-J, Li C, Li Y-Y, Zhuo R-X, Zhang X-Z (2013) Novel shell-cross-linked micelles with detachable PEG corona for glutathione-mediated intracellular drug delivery. Soft Matter 9(3):692–699

    Article  CAS  Google Scholar 

  26. Jiang X, Chen J, Bajić A, Zhang C, Song X, Carroll SL, Cai Z-L, Tang M, Xue M, Cheng N (2017) Quantitative real-time imaging of glutathione. Nat Commun 8(16087):16087

    Article  CAS  Google Scholar 

  27. Trachootham D, Alexandre J, Huang P (2009) Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach? Nat Rev Drug Discov 8(7):579–591

    Article  CAS  Google Scholar 

  28. Chen Z, Wan L, Yuan Y, Kuang Y, Xu X, Liao T, Liu J, Xu Z-Q, Jiang B, Li C (2020) pH/GSH-dual-sensitive hollow mesoporous silica nanoparticle-based drug delivery system for targeted cancer therapy. ACS Biomater Sci Eng 6(6):3375–3387

    Article  CAS  Google Scholar 

  29. 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(1):6907

    Article  CAS  Google Scholar 

  30. Ponraj T, Vivek R, Paulpandi M, Rejeeth C, Nipun Babu V, Vimala K, Anand K, Sivaselvam S, Vasanthakumar A, Ponpandian N, Kannan S (2018) Mitochondrial dysfunction-induced apoptosis in breast carcinoma cells through a pH-dependent intracellular quercetin NDDS of PVPylated-TiO2NPs. J Mater Chem B 6(21):3555–3570

    Article  CAS  Google Scholar 

  31. Panieri E, Santoro MM (2016) ROS homeostasis and metabolism: a dangerous liason in cancer cells. Cell Death Dis 7(6):e2253–e2253

    Article  CAS  Google Scholar 

  32. Friedman JR, Nunnari J (2014) Mitochondrial form and function. Nature 505(7483):335–343

    Article  CAS  Google Scholar 

  33. Xu Z, Chen X, Sun Z, Li C, Jiang B (2019) Recent progress on mitochondrial targeted cancer therapy based on inorganic nanomaterials. Mater Today Chem 12:240–260

    Article  CAS  Google Scholar 

  34. Thangam R, Sathuvan M, Poongodi A, Suresh V, Pazhanichamy K, Sivasubramanian S, Kanipandian N, Ganesan N, Rengasamy R, Thirumurugan R, Kannan S (2014) Activation of intrinsic apoptotic signaling pathway in cancer cells by Cymbopogon citratus polysaccharide fractions. Carbohyd Polym 107:138–150

    Article  CAS  Google Scholar 

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Funding

We received financial support from the National Natural Science Foundation of China (22073025, 21603067) and Hubei Nature Science Foundation of China (2019CFB748).

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Authors and Affiliations

  1. Ministry-of-Education Key Laboratory for the Green Preparation and Application of Functional Materials, Collaborative Innovation Center for Advanced Organic Chemical Materials Co-constructed by the Province and Ministry, Hubei Key Laboratory of Polymer Materials, School of Materials Science & Engineering, Hubei University, Wuhan, 430062, China

    Hang He, Qingyuan Yang, Haimin Li, Song Meng, Ziqiang Xu, Xueqin Chen, Zhengguang Sun, Bingbing Jiang & Cao Li

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  1. Hang He
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  2. Qingyuan Yang
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  3. Haimin Li
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  7. Zhengguang Sun
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  9. Cao Li
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Correspondence to Ziqiang Xu or Cao Li.

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He, H., Yang, Q., Li, H. et al. Hollow mesoporous MnO2-carbon nanodot-based nanoplatform for GSH depletion enhanced chemodynamic therapy, chemotherapy, and normal/cancer cell differentiation. Microchim Acta 188, 141 (2021). https://doi.org/10.1007/s00604-021-04801-5

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