Skip to main content
Log in

Chemotactic nanomotor for multimodal combined therapy of glioblastoma

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

Abstract

Glioblastoma (GBM) is the most aggressive malignant brain tumor. Due to the infiltration and heterogeneity of GBM, the obstruction of the blood-brain barrier (BBB) and the unique immunosuppressive mechanism, it is hard to achieve significant effects of GBM treatment. Here, a kind of chemotactic nanomotor that loaded with glucose oxidase (GOx) and carboxylated cisplatin (Pt(IV)) prodrug on the L-arginine-derived polymer is proposed. The nanomotors are driven by catalysis of glucose decomposition and the positive chemotaxis towards the GBM microenvironment where inducible nitric oxide synthase and reactive oxygen species are highly expressed. This facilitates the BBB crossing and GBM targeting of the nanomotors. In addition, the released nitric oxide (NO) during propulsion as well as the loaded GOx and Pt(IV) can exert combined NO/starvation/chemotherapy. Meanwhile, it is able to induce and enhance the immune response through multiple pathways, thus better coping with the complexities of GBM treatment.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Barbosa BJAP, Mariano ED, Batista CM, Marie SKN, Teixeira MJ, Pereira CU, Tatagiba MS, Lepski GA. Neurosurg Rev, 2015, 38: 217–227

    Article  PubMed  Google Scholar 

  2. Jiang T, Mao Y, Ma W, Mao Q, You Y, Yang X, Jiang C, Kang C, Li X, Chen L, Qiu X, Wang W, Li W, Yao Y, Li S, Li S, Wu A, Sai K, Bai H, Li G, Chen B, Yao K, Wei X, Liu X, Zhang Z, Dai Y, Lv S, Wang L, Lin Z, Dong J, Xu G, Ma X, Cai J, Zhang W, Wang H, Chen L, Zhang C, Yang P, Yan W, Liu Z, Hu H, Chen J, Liu Y, Yang Y, Wang Z, Wang Z, Wang Y, You G, Han L, Bao Z, Liu Y, Wang Y, Fan X, Liu S, Liu X, Wang Y, Wang Q. Cancer Lett, 2016, 375: 263–273

    Article  CAS  PubMed  Google Scholar 

  3. Shergalis A, Bankhead A, Luesakul U, Muangsin N, Neamati N. Pharmacol Rev, 2018, 70: 412–445

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Farooque A, Mathur R, Verma A, Kaul V, Bhatt AN, Adhikari JS, Afrin F, Singh S, Dwarakanath BS. Expert Rev Anticancer Ther, 2011, 11: 791–802

    Article  CAS  PubMed  Google Scholar 

  5. Pollycove M. Environ Health Perspect, 1998, 106: 363–368

    PubMed  PubMed Central  Google Scholar 

  6. Goellner EM, Grimme B, Brown AR, Lin YC, Wang XH, Sugrue KF, Mitchell L, Trivedi RN, Tang J, Sobol RW. Cancer Res, 2011, 71: 2308–2317

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Chen J, Li Y, Yu TS, McKay RM, Burns DK, Kernie SG, Parada LF. Nature, 2012, 488: 522–526

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Di Mascolo D, Palange AL, Primavera R, Macchi F, Catelani T, Piccardi F, Spanò R, Ferreira M, Marotta R, Armirotti A, Gallotti AL, Galli R, Wilson C, Grant GA, Decuzzi P. Nat Nanotechnol, 2021, 16: 820–829

    Article  CAS  PubMed  Google Scholar 

  9. Wang Y, Jiang Y, Wei D, Singh P, Yu Y, Lee T, Zhang L, Mandl HK, Piotrowski-Daspit AS, Chen X, Li F, Li X, Cheng Y, Josowitz A, Yang F, Zhao Y, Wang F, Zhao Z, Huttner A, Bindra RS, Xiao H, Mark Saltzman W. Nat Biomed Eng, 2021, 5: 1048–1058

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Graham J, Muhsin M, Kirkpatrick P. Nat Rev Drug Discov, 2004, 3: 11–12

    Article  CAS  PubMed  Google Scholar 

  11. Wong DYQ, Ong WWF, Ang WH. Angew Chem Int Ed, 2015, 54: 6483–6487

    Article  CAS  Google Scholar 

  12. Peng J, Cui Y, Xu S, Wu X, Huang Y, Zhou W, Wang S, Fu Z, Xie H. Oncol Lett, 2021, 21: 369

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Fan W, Lu N, Huang P, Liu Y, Yang Z, Wang S, Yu G, Liu Y, Hu J, He Q, Qu J, Wang T, Chen X. Angew Chem Int Ed, 2017, 56: 1229–1233

    Article  CAS  Google Scholar 

  14. Lawless SJ, Kedia-Mehta N, Walls JF, McGarrigle R, Convery O, Sinclair LV, Navarro MN, Murray J, Finlay DK. Nat Commun, 2017, 8: 15620

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Tarr JM, Young PJ, Morse R, Shaw DJ, Haigh R, Petrov PG, Johnson SJ, Winyard PG, Eggleton P. J Mol Biol, 2010, 401: 799–812

    Article  CAS  PubMed  Google Scholar 

  16. Men Y, Peng S, Yang P, Jiang Q, Zhang Y, Shen B, Dong P, Pang Z, Yang W. ACS Appl Mater Interfaces, 2018, 10: 23509–23521

    Article  CAS  PubMed  Google Scholar 

  17. Kim Y, Binauld S, Stenzel MH. Biomacromolecules, 2012, 13: 3418–3426

    Article  CAS  PubMed  Google Scholar 

  18. Huang X, Huang Y. Chin Chem Lett, 2015, 26: 636–640

    Article  CAS  Google Scholar 

  19. Liu J, Guo X, Luo Z, Zhang J, Li M, Cai K. Nanoscale, 2018, 10: 13737–13750

    Article  CAS  PubMed  Google Scholar 

  20. Shahbazi MA, Almeida PV, Mäkilä EM, Kaasalainen MH, Salonen JJ, Hirvonen JT, Santos HA. Biomaterials, 2014, 35: 7488–7500

    Article  CAS  PubMed  Google Scholar 

  21. Polzer F, Heigl J, Schneider C, Ballauff M, Borisov OV. Macromolecules, 2011, 44: 1654–1660

    Article  CAS  Google Scholar 

  22. Fan L, Wang X, Cao Q, Yang Y, Wu D. Biomater Sci, 2019, 7: 1984–1994

    Article  CAS  PubMed  Google Scholar 

  23. Wu DQ, Zhu J, Han H, Zhang JZ, Wu FF, Qin XH, Yu JY. Acta Biomater, 2018, 65: 305–316

    Article  CAS  PubMed  Google Scholar 

  24. Sun K, Tang Y, Li Q, Yin S, Qin W, Yu J, Chiu DT, Liu Y, Yuan Z, Zhang X, Wu C. ACS Nano, 2016, 10: 6769–6781

    Article  CAS  PubMed  Google Scholar 

  25. Chang K, Liu Z, Fang X, Chen H, Men X, Yuan Y, Sun K, Zhang X, Yuan Z, Wu C. Nano Lett, 2017, 17: 4323–4329

    Article  CAS  PubMed  Google Scholar 

  26. Zhang G, Zhang L, Si Y, Li Q, Xiao J, Wang B, Liang C, Wu Z, Tian G. Chem Eng J, 2020, 388: 124269

    Article  CAS  Google Scholar 

  27. Shi Y, Liu SA, Kerwood DJ, Goodisman J, Dabrowiak JC. J Inorg Biochem, 2012, 107: 6–14

    Article  CAS  PubMed  Google Scholar 

  28. Park SS, Jung MH, Lee YS, Bae JH, Kim SH, Ha CS. Mater Des, 2019, 184: 108187

    Article  CAS  Google Scholar 

  29. Shen Z, Liu T, Li Y, Lau J, Yang Z, Fan W, Zhou Z, Shi C, Ke C, Bregadze VI, Mandal SK, Liu Y, Li Z, Xue T, Zhu G, Munasinghe J, Niu G, Wu A, Chen X. ACS Nano, 2018, 12: 11355–11365

    Article  CAS  PubMed  Google Scholar 

  30. Li T, Liu Z, Hu J, Chen L, Chen T, Tang Q, Yu B, Zhao B, Mao C, Wan M. Adv Mater, 2022, 34: 2206654

    Article  CAS  Google Scholar 

  31. Ye F, Zhang B, Qiu L, Zhang Y, Zhang Y, Zhang J, Zhao Q, Lu L, Zhang Z. Mater Today Bio, 2022, 16: 100408

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Chelliah SS, Paul EAL, Kamarudin MNA, Parhar I. Molecules, 2021, 26: 1169

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Lin KH, Hong ST, Wang HT, Lo YL, Lin A, Yang J. Int J Mol Sci, 2016, 17: 1998

    Article  PubMed  PubMed Central  Google Scholar 

  34. Wang Q, Li T, Yang J, Zhao Z, Tan K, Tang S, Wan M, Mao C. Adv Mater, 2022, 34: 2201406

    Article  CAS  Google Scholar 

  35. Munger MA, Radwanski P, Hadlock GC, Stoddard G, Shaaban A, Falconer J, Grainger DW, Deering-Rice CE. Nanomed-Nanotechnol Biol Med, 2014, 10: 1–9

    Article  CAS  Google Scholar 

  36. Yang W, Wang L, Mettenbrink EM, DeAngelis PL, Wilhelm S. Annu Rev Pharmacol Toxicol, 2021, 61: 269–289

    Article  CAS  PubMed  Google Scholar 

  37. Menges M, Roßner S, Voigtlander C, Schindler H, Kukutsch NA, Bogdan C, Erb K, Schuler G, Lutz MB. J Exp Med, 2002, 195: 15–22

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Shao Q, Ning H, Lv J, Liu Y, Zhao X, Ren G, Feng A, Xie Q, Sun J, Song B, Yang Y, Gao W, Ding K, Yang M, Hou M, Peng J, Qu X. Blood, 2012, 119: 4636–4644

    Article  CAS  PubMed  Google Scholar 

  39. Bo R, Liu Z, Zhang J, Gu P, Ou N, Sun Y, Hu Y, Liu J, Wang D. Carbohydrate Polyms, 2019, 205: 540–549

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Natural Science Foundation of China (22175096, 22275095), the Social Development Project of Jiangsu Natural Science Foundation (BE2019744), the Qinglan Project Foundation of Colleges and Universities of Jiangsu Province, the Jiangsu Collaborative Innovation Center of Biomedical Functional Materials, the Priority Academic Program Development of Jiangsu Higher Education Institution, the Postgraduate Research & Practice Innovation Program of Jiangsu Province (KYCX22_1545).

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Chun Mao, Jian Shen or 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 chem.scichina.com and 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 for

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, T., Chen, L., Xue, Y. et al. Chemotactic nanomotor for multimodal combined therapy of glioblastoma. Sci. China Chem. 67, 1277–1288 (2024). https://doi.org/10.1007/s11426-023-1837-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11426-023-1837-7

Navigation