Skip to main content
SpringerLink
Log in

GSH-induced chemotaxis nanomotors for cancer treatment by ferroptosis strategy

  • Articles
  • Published:
Science China Chemistry Aims and scope Submit manuscript

Abstract

Overexpression of glutathione (GSH) in tumor cells greatly inhibits the therapy effect of traditional ferroptosis inducers; thus, control of the GSH level is an important way to improve the efficacy of ferroptosis. Herein, a kind of nanomotor based on metal organic framework material NH2-MIL-101 is constructed, in which polyethylene glycol (PEG) and glutathione hydrolase γ-glutamyltransferase (GGT) are asymmetrically modified to obtain mPEG@MIL-101@GGT nanomotors (PMG NMs). The nanomotor proposed in this article can be induced by overexpressing GSH in tumors to form chemotactic effects through the specific affinity between enzymes and substrates. Results indicate that the tail structure provided by PEG and the affinity between GGT and GSH can enable the stable chemotaxis behavior of nanomotors in a complex environment, thus enriching and penetrating deeply at the tumor site. In addition, after loading the ferroptosis inducer Erastin, the system shows a highly effective induction effect of tumor ferroptosis. Erastin in the system can effectively inhibit the synthesis of GSH, and PMG NMS can react with GSH through Fe3+ and GGT to promote GSH depletion. The produced Fe2+ can generate excessive reactive oxygen species through Fenton reaction, which further promotes the death of tumor cells. Meantime, the chemotaxis behavior of the nanomotors based on the endogenous biochemical reaction of GGT-catalyzed GSH hydrolysis can endow nanomotors with the enhanced delivery and penetration ability in tumors, thus collaboratively enhancing the ferroptosis effect. This strategy designed according to the physiological characteristics of tumors has good biosafety and treatment effect, providing new perspectives for micro/nanomotor and tumor treatment.

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

Similar content being viewed by others

References

  1. Wu J, Minikes AM, Gao M, Bian H, Li Y, Stockwell BR, Chen ZN, Jiang X. Nature, 2019, 572: 402–406

    Article  CAS  Google Scholar 

  2. Yi J, Zhu J, Wu J, Thompson CB, Jiang X. Proc Natl Acad Sci USA, 2020, 117: 31189–31197

    Article  CAS  Google Scholar 

  3. Doll S, Freitas FP, Shah R, Aldrovandi M, da Silva MC, Ingold I, Goya Grocin A, Xavier da Silva TN, Panzilius E, Scheel CH, Mourão A, Buday K, Sato M, Wanninger J, Vignane T, Mohana V, Rehberg M, Flatley A, Schepers A, Kurz A, White D, Sauer M, Sattler M, Tate EW, Schmitz W, Schulze A, O’Donnell V, Proneth B, Popowicz GM, Pratt DA, Angeli JPF, Conrad M. Nature, 2019, 575: 693–698

    Article  CAS  Google Scholar 

  4. Shen Z, Song J, Yung BC, Zhou Z, Wu A, Chen X. Adv Mater, 2018, 30: 1704007

    Article  Google Scholar 

  5. Zhou Z, Wu H, Yang R, Xu A, Zhang Q, Dong J, Qian C, Sun M. Sci Adv, 2020, 6: eabc4373

    Article  CAS  Google Scholar 

  6. Sun Y, Zheng Y, Wang C, Liu Y. Cell Death Dis, 2018, 9: 753

    Article  Google Scholar 

  7. Zheng J, Conrad M. Cell Metab, 2020, 32: 920–937

    Article  CAS  Google Scholar 

  8. Zheng DW, Lei Q, Zhu JY, Fan JX, Li CX, Li C, Xu Z, Cheng SX, Zhang XZ. Nano Lett, 2017, 17: 284–291

    Article  CAS  Google Scholar 

  9. Du JZ, Li HJ, Wang J. Acc Chem Res, 2018, 51: 2848–2856

    Article  CAS  Google Scholar 

  10. Wan M, Chen H, Wang Q, Niu Q, Xu P, Yu Y, Zhu T, Mao C, Shen J. Nat Commun, 2019, 10: 966

    Article  Google Scholar 

  11. Meng F, Hennink WE, Zhong Z. Biomaterials, 2009, 30: 2180–2198

    Article  CAS  Google Scholar 

  12. Wang L, Hortelão AC, Huang X, Sánchez S. Angew Chem Int Ed, 2019, 58: 7992–7996

    Article  CAS  Google Scholar 

  13. Wan M, Li T, Chen H, Mao C, Shen J. Angew Chem Int Ed, 2021, 60: 13158–13176

    Article  CAS  Google Scholar 

  14. Tang J, Yao C, Gu Z, Jung S, Luo D, Yang D. Angew Chem Int Ed, 2020, 59: 2490–2495

    Article  CAS  Google Scholar 

  15. Schmidt CK, Medina-Sánchez M, Edmondson RJ, Schmidt OG. Nat Commun, 2020, 11: 5618

    Article  CAS  Google Scholar 

  16. Wan MM, Chen H, Da Wang Z, Liu ZY, Yu YQ, Li L, Miao ZY, Wang XW, Wang Q, Mao C, Shen J, Wei J. Adv Sci, 2021, 8: 2002525

    Article  CAS  Google Scholar 

  17. Wan M, Liu Z, Li T, Chen H, Wang Q, Chen T, Tao Y, Mao C. Angew Chem Int Ed, 2021, 60: 16139–16148

    Article  CAS  Google Scholar 

  18. Chen H, Shi T, Wang Y, Liu Z, Liu F, Zhang H, Wang X, Miao Z, Liu B, Wan M, Mao C, Wei J. J Am Chem Soc, 2021, 143: 12025–12037

    Article  CAS  Google Scholar 

  19. Zhou Q, Shao S, Wang J, Xu C, Xiang J, Piao Y, Zhou Z, Yu Q, Tang J, Liu X, Gan Z, Mo R, Gu Z, Shen Y. Nat Nanotechnol, 2019, 14: 799–809

    Article  CAS  Google Scholar 

  20. Wang G, Zhou Z, Zhao Z, Li Q, Wu Y, Yan S, Shen Y, Huang P. ACS Nano, 2020, 14: 4890–4904

    Article  CAS  Google Scholar 

  21. Sengupta S, Dey KK, Muddana HS, Tabouillot T, Ibele ME, Butler PJ, Sen A. J Am Chem Soc, 2013, 135: 1406–1414

    Article  CAS  Google Scholar 

  22. Sengupta S, Spiering MM, Dey KK, Duan W, Patra D, Butler PJ, Astumian RD, Benkovic SJ, Sen A. ACS Nano, 2014, 8: 2410–2418

    Article  CAS  Google Scholar 

  23. Horcajada P, Chalati T, Serre C, Gillet B, Sebrie C, Baati T, Eubank JF, Heurtaux D, Clayette P, Kreuz C, Chang JS, Hwang YK, Marsaud V, Bories PN, Cynober L, Gil S, Férey G, Couvreur P, Gref R. Nat Mater, 2010, 9: 172–178

    Article  CAS  Google Scholar 

  24. Huo M, Wang L, Chen Y, Shi J. Nat Commun, 2017, 8: 357

    Article  Google Scholar 

  25. Lee TC, Alarcón-Correa M, Miksch C, Hahn K, Gibbs JG, Fischer P. Nano Lett, 2014, 14: 2407–2412

    Article  CAS  Google Scholar 

  26. Bockuviene A, Balciunaite J, Slavuckyte K, Zaliauskiene L, Vareikis A, Makuska R. J Polym Res, 2015, 23: 10

    Article  Google Scholar 

  27. Ji Y, Lin X, Wu Z, Wu Y, Gao W, He Q. Angew Chem Int Ed, 2019, 58: 12200–12205

    Article  CAS  Google Scholar 

  28. Hortelao AC, Simó C, Guix M, Guallar-Garrido S, Julián E, Vilela D, Rejc L, Ramos-Cabrer P, Cossío U, Gómez-Vallejo V, Patiño T, Llop J, Sánchez S. Sci Robot, 2021, 6: eabd2823

    Article  Google Scholar 

  29. Glidden M, Muschol M. J Phys Chem C, 2012, 116: 8128–8137

    Article  CAS  Google Scholar 

  30. Xuan M, Wu Z, Shao J, Dai L, Si T, He Q. J Am Chem Soc, 2016, 138: 6492–6497

    Article  CAS  Google Scholar 

  31. Cheng R, Feng F, Meng F, Deng C, Feijen J, Zhong Z. J Control Release, 2011, 152: 2–12

    Article  CAS  Google Scholar 

  32. Circu ML, Stringer S, Rhoads CA, Moyer MP, Aw TY. Biochem Pharmacol, 2009, 77: 76–85

    Article  CAS  Google Scholar 

  33. Brechbuhl HM, Gould N, Kachadourian R, Riekhof WR, Voelker DR, Day BJ. J Biol Chem, 2010, 285: 16582–16587

    Article  CAS  Google Scholar 

  34. Franco R, Schoneveld OJ, Pappa A, Panayiotidis MI. Arch Physiol Biochem, 2007, 113: 234–258

    Article  CAS  Google Scholar 

  35. Chaiswing L, Zhong W, Liang Y, Jones DP, Oberley TD. Free Radical Biol Med, 2012, 52: 452–461

    Article  CAS  Google Scholar 

  36. Shi L, Wu W, Duan Y, Xu L, Xu Y, Hou L, Meng X, Zhu X, Liu B. Angew Chem Int Ed, 2020, 59: 19168–19174

    Article  CAS  Google Scholar 

  37. Cai L, Yang C, Jia W, Liu Y, Xie R, Lei T, Yang Z, He X, Tong R, Gao H. Adv Funct Mater, 2020, 30: 1909999

    Article  CAS  Google Scholar 

  38. Martínez-Menárguez JA. ISRN Cell Biol, 2013, 2013: 1–15

    Article  Google Scholar 

  39. Iversen TG, Frerker N, Sandvig K. J Nanobiotechnol, 2012, 10: 33

    Article  CAS  Google Scholar 

  40. Chen Y, Li ZH, Pan P, Hu JJ, Cheng SX, Zhang XZ. Adv Mater, 2020, 32: 2001452

    Article  CAS  Google Scholar 

  41. Ma X, Ren X, Guo X, Fu C, Wu Q, Tan L, Li H, Zhang W, Chen X, Zhong H, Meng X. Biomaterials, 2019, 214: 119223

    Article  CAS  Google Scholar 

  42. Battaglia AM, Chirillo R, Aversa I, Sacco A, Costanzo F, Biamonte F. Cells, 2020, 9: 1505

    Article  CAS  Google Scholar 

  43. Li Y, Xia J, Shao F, Zhou Y, Yu J, Wu H, Du J, Ren X. Biochem Biophysl Res Commun, 2021, 534: 877–884

    Article  CAS  Google Scholar 

  44. Niedernhofer LJ, Daniels JS, Rouzer CA, Greene RE, Marnett LJ. J Biol Chem, 2003, 278: 31426–31433

    Article  CAS  Google Scholar 

  45. Yu C, Zhou Z, Wang J, Sun J, Liu W, Sun Y, Kong B, Yang H, Yang S. J Hazard Mater, 2015, 283: 519–528

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Natural Science Foundation of China (22175096), the Social Development Project of Jiangsu Natural Science Foundation (BE2019744), the Collaborative Innovation Center of Biomedical Functional Materials, and the Priority Academic Program Development of Jiangsu Higher Education Institution.

Author information

Author notes

  1. These authors contributed equally to this work.

Authors and Affiliations

  1. National and Local Joint Engineering Research Center of Biomedical Functional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Nanjing, 210023, China

    Zhiyong Liu, Ting Li, Nan Li, Yujing Wang, Lin Chen, Xueting Tang, Mimi Wan & Chun Mao

Authors
  1. Zhiyong Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ting Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nan Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yujing Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lin Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Xueting Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Mimi Wan
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Chun Mao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mimi Wan.

Ethics declarations

Conflict of interest The authors declare no conflict of interest.

Additional information

Supporting information The supporting information is available online at http://chem.scichina.com and http://link.springer.com/journal/11426. The supporting materials are published as submitted, without typesetting or editing. The responsibility for scientific accuracy and content remains entirely with the authors.

Supporting Information

GSH-induced chemotaxis nanomotors for cancer treatment by ferroptosis strategy

Supplementary material, approximately 18.0 MB.

Supplementary material, approximately 23.8 MB.

Supplementary material, approximately 2.01 MB.

Supplementary material, approximately 4.20 MB.

Supplementary material, approximately 472 KB.

Supplementary material, approximately 4.50 MB.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liu, Z., Li, T., Li, N. et al. GSH-induced chemotaxis nanomotors for cancer treatment by ferroptosis strategy. Sci. China Chem. 65, 989–1002 (2022). https://doi.org/10.1007/s11426-021-1208-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11426-021-1208-6

Keywords

Search

Navigation