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Polymer-based synthetic oncolytic virus-like nanoparticles for cancer immunotherapy

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Abstract

Oncolytic viruses have emerged as new powerful therapeutic agents for cancer therapy by specifically lysing cancer cells while activating innate immune responses at the same time. However, due to the thorny issues of safety concerns and host immune reaction, the clinical application of oncolytic viruses is still limited. Herein, we report a rationally designed oncolytic virus-like nanoparticles (OV-NPs) composed of stimulator of interferon genes (STING)-stimulating polymer loaded with therapeutic genes for cancer immunotherapy. After injection into tumor, the OV-NPs carrying OX40L plasmid could reprogram tumor cells to express OX40L immune checkpoint molecules and activate the STING pathway for cooperatively enhancing antitumor immunity, with a tumor suppression rate of 92.3% in B16F10 tumor model and 78.7% in MC38 tumor model without causing any toxicity. The OV-NPs could be further applied in carrying other plasmids (IL-12) and utilization in gene combination therapy. This study should inspire designing synthetic OV-NPs as alternative strategies for extending oncolytic virus application in cancer immunotherapy.

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References

  1. Fukuhara H, Ino Y, Todo T. Cancer Sci, 2016, 107: 1373–1379

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  2. Kumar S, Gao L, Yeagy B, Reid T. Curr Opi Mol Ther, 2008, 10: 371–379

    Google Scholar 

  3. Russell L, Peng KW. Chin Clin Oncol, 2018, 7: 16

    Article  PubMed  PubMed Central  Google Scholar 

  4. Woller N, Gurlevik E, Ureche CI, Schumacher A, Kuhnel F. Front Oncol, 2014, 4: 188

    Article  PubMed  PubMed Central  Google Scholar 

  5. Chen DS, Mellman I. Immunity, 2013, 39: 1–10

    Article  PubMed  Google Scholar 

  6. Taguchi S, Fukuhara H, Todo T. Jpnese J Clin Oncol, 2019, 49: 201–209

    Article  Google Scholar 

  7. Koch M, Lawler S, Chiocca E. Cancers, 2020, 12: 3514

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Li L, Liu S, Han D, Tang B, Ma J. Front Oncol, 2020, 10: 475

    Article  PubMed  PubMed Central  Google Scholar 

  9. Kaufman HL, Kohlhapp FJ, Zloza A. Nat Rev Drug Discov, 2015, 14: 642–662

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Chen H, Gu Z, An H, Chen C, Chen J, Cui R, Chen S, Chen W, Chen X, Chen X, Chen Z, Ding B, Dong Q, Fan Q, Fu T, Hou D, Jiang Q, Ke H, Jiang X, Liu G, Li S, Li T, Liu Z, Nie G, Ovais M, Pang D, Qiu N, Shen Y, Tian H, Wang C, Wang H, Wang Z, Xu H, Xu JF, Yang X, Zhu S, Zheng X, Zhang X, Zhao Y, Tan W, Zhang X, Zhao Y. Sci China Chem, 2018, 61: 1503–1552

    Article  CAS  Google Scholar 

  11. Chen WH, Chen QW, Chen Q, Cui C, Duan S, Kang Y, Liu Y, Liu Y, Muhammad W, Shao S, Tang C, Wang J, Wang L, Xiong MH, Yin L, Zhang K, Zhang Z, Zhen X, Feng J, Gao C, Gu Z, He C, Ji J, Jiang X, Liu W, Liu Z, Peng H, Shen Y, Shi L, Sun X, Wang H, Wang J, Xiao H, Xu FJ, Zhong Z, Zhang XZ, Chen X. Sci China Chem, 2022, 65: 1010–1075

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Xu Y, Ma S, Zhao J, Chen H, Si X, Huang Z, Yu Z, Song W, Tang Z, Chen X. Biomaterials, 2022, 284: 121489

    Article  PubMed  CAS  Google Scholar 

  13. Ma S, Song W, Xu Y, Si X, Zhang Y, Tang Z, Chen X. CCS Chem, 2020, 2: 390–400

    Article  CAS  Google Scholar 

  14. Chattopadhyay S, Chen JY, Chen HW, Hu CMJ. Nanotheranostics, 2017, 1: 244–260

    Article  PubMed  PubMed Central  Google Scholar 

  15. Jeevanandam J, Pal K, Danquah MK. Biochimie, 2019, 157: 38–47

    Article  PubMed  CAS  Google Scholar 

  16. Twumasi-Boateng K, Pettigrew JL, Kwok YYE, Bell JC, Nelson BH. Nat Rev Cancer, 2018, 18: 526

    Article  PubMed  CAS  Google Scholar 

  17. Somiya M, Liu Q, Kuroda S. Nanotheranostics, 2017, 1: 415–429

    Article  PubMed  PubMed Central  Google Scholar 

  18. Maslanka Figueroa S, Fleischmann D, Goepferich A. J Control Release, 2021, 329: 552–569

    Article  PubMed  CAS  Google Scholar 

  19. Wu F, Li Y, Meng Y, Cai X, Shi J, Li J, Chen Y, Zhang L, Meng X, Li H, Jiang X, Fu Z, Wu Y, Bu W. Angew Chem Int Ed, 2022, 61: e202210487

    Article  CAS  Google Scholar 

  20. Li Y, Su Z, Zhao W, Zhang X, Momin N, Zhang C, Wittrup KD, Dong Y, Irvine DJ, Weiss R. Nat Cancer, 2020, 1: 882–893

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Huang KW, Hsu FF, Qiu JT, Chern GJ, Lee YA, Chang CC, Huang YT, Sung YC, Chiang CC, Huang RL, Lin CC, Dinh TK, Huang HC, Shih YC, Alson D, Lin CY, Lin YC, Chang PC, Lin SY, Chen Y. Sci Adv, 2020, 6: eaax5032

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Wannasarit S, Wang S, Figueiredo P, Trujillo C, Eburnea F, Simón-Gracia L, Correia A, Ding Y, Teesalu T, Liu D, Wiwattanapatapee R, Santos HA, Li W. Adv Funct Mater, 2019, 29: 1905352

    Article  CAS  Google Scholar 

  23. Si XH, Song WT, Chen XS. Acta Polym Sin, 2023, 54: 837–852

    CAS  Google Scholar 

  24. Dong S, Ma S, Liu ZL, Ma LL, Zhang Y, Tang ZH, Deng MX, Song WT. Chin J Polym Sci, 2021, 39: 865–873

    Article  CAS  Google Scholar 

  25. Zhu ZY, Song WT, Chen XS. Acta Polym Sin, 2023, 54: 534–549

    CAS  Google Scholar 

  26. Zhao J, Liu L, Wang Y, Huang Z, Zhang Y, Qiao R, Davis T, Tang Z, Song W, Chen X. CCS Chem, 2023, doi: https://doi.org/10.31635/ccschem.023.202303214

  27. Liu L, Zhao J, Huang Z, Xu Y, Chen H, Qiao R, Song W, Tang Z, Davis T, Chen X. Fund Res, 2023, doi: https://doi.org/10.1016/j.fmre.2023.1003.1018

  28. Zhao J, Xu Y, Ma S, Wang Y, Huang Z, Qu H, Yao H, Zhang Y, Wu G, Huang L, Song W, Tang Z, Chen X. Adv Mater, 2022, 34: e2109254

    Article  PubMed  Google Scholar 

  29. Gao Y, Zhao J, Huang Z, Zhao H, Guo Z, Ma S, Tang X, Song W, Chen X. ACS Biomater Sci Eng, 2023, 9: 4108–4116

    Article  PubMed  CAS  Google Scholar 

  30. Zhang Y, Ma S, Liu X, Xu Y, Zhao J, Si X, Li H, Huang Z, Wang Z, Tang Z, Song W, Chen X. Adv Mater, 2021, 33: e2007293

    Article  PubMed  Google Scholar 

  31. Jalah R, Rosati M, Ganneru B, Pilkington GR, Valentin A, Kulkarni V, Bergamaschi C, Chowdhury B, Zhang GM, Beach RK, Alicea C, Broderick KE, Sardesai NY, Pavlakis GN, Felber BK. J Biol Chem, 2013, 288: 6763–6776

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Vaughan HJ, Green JJ, Tzeng SY. Adv Mater, 2020, 32: e1901081

    Article  PubMed  Google Scholar 

  33. Huang Z, Song W, Chen X. Front Chem, 2020, 8: 380

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  34. Guo JF, Yu Z, Sun DD, Zou YF, Liu Y, Huang L. Mol Cancer, 2021, doi: https://doi.org/10.1186/s12943-020-01297-0

  35. Song W, Shen L, Wang Y, Liu Q, Goodwin TJ, Li J, Dorosheva O, Liu T, Liu R, Huang L. Nat Commun, 2018, 9: 2237

    Article  PubMed  PubMed Central  Google Scholar 

  36. Wang Y, Song W, Hu M, An S, Xu L, Li J, Kinghorn KA, Liu R, Huang L. Adv Funct Mater, 2018, 28: 1802847

    Article  Google Scholar 

  37. Webb GJ, Hirschfield GM, Lane PJL. Clinic Rev Allerg Immunol, 2016, 50: 312–332

    Article  CAS  Google Scholar 

  38. Li S, Luo M, Wang Z, Feng Q, Wilhelm J, Wang X, Li W, Wang J, Cholka A, Fu Y, Sumer BD, Yu H, Gao J. Nat Biomed Eng, 2021, 5: 455–466

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. Zhang C, Shang G, Gui X, Zhang X, Bai X, Chen ZJ. Nature, 2019, 567: 394–398

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  40. Pagenstecher A, Lassmann S, Carson MJ, Kincaid CL, Stalder AK, Campbell IL. J Immunol, 2000, 164: 4481–4492

    Article  PubMed  CAS  Google Scholar 

  41. Nguyen KG, Vrabel MR, Mantooth SM, Hopkins JJ, Wagner ES, Gabaldon TA, Zaharoff DA. Front Immunol, 2020, 11: 575597

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. Mansurov A, Ishihara J, Hosseinchi P, Potin L, Marchell TM, Ishihara A, Williford JM, Alpar AT, Raczy MM, Gray LT, Swartz MA, Hubbell JA. Nat Biomed Eng, 2020, 4: 531–543

    Article  PubMed  CAS  Google Scholar 

  43. Wang P, Li X, Wang J, Gao D, Li Y, Li H, Chu Y, Zhang Z, Liu H, Jiang G, Cheng Z, Wang S, Dong J, Feng B, Chard LS, Lemoine NR, Wang Y. Nat Commun, 2017, 8: 1395

    Article  PubMed  PubMed Central  Google Scholar 

  44. Farkona S, Diamandis EP, Blasutig IM. BMC Med, 2016, 14: 73

    Article  PubMed  PubMed Central  Google Scholar 

  45. Si X, Ji G, Ma S, Xu Y, Zhao J, Zhang Y, Huang Z, Tang Z, Song W, Chen X. Adv Healthc Mater, 2021, 10: e2100862

    Article  PubMed  Google Scholar 

  46. Liang JL, Luo GF, Chen WH, Zhang XZ. Adv Mater, 2021, 33: e2007630

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Natural Science Foundation of China (22222509, 52025035, 51973215, 22375198, 52103194), Bureau of International Cooperation Chinese Academy of Sciences (121522KYSB20200029), Jilin Province Science and Technology Development Plan (YDZJ202101ZYTS131, 20220402037GH, 20210508049RQ), Jilin Provincial International Cooperation Key Laboratory of Biomedical Polymers (20210504001GH), Changchun Science and Technology Development Plan (21ZY09, 21ZGY30), the China Post-doctoral Science Foundation (E21S2101), the Youth Talents Promotion Project of Jilin Province (QT202103), and the Youth Innovation Promotion Association of Chinese Academy of Sciences (2020232).

Author information

Authors and Affiliations

  1. State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun, 130012, China

    Yuxi Gao & Xuesi Chen

  2. Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China

    Yuxi Gao, Hanqin Zhao, Jiayu Zhao, Sheng Ma, Xinghui Si, Liping Liu, Wantong Song & Xuesi Chen

  3. School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei, 230026, China

    Hanqin Zhao, Jiayu Zhao, Liping Liu, Wantong Song & Xuesi Chen

  4. Australian Institute of Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Queensland, 4072, Australia

    Ruirui Qiao

  5. Jilin Biomedical Polymers Engineering Laboratory, Changchun, 130022, China

    Sheng Ma, Xinghui Si, Wantong Song & Xuesi Chen

Authors
  1. Yuxi Gao
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  2. Hanqin Zhao
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  3. Jiayu Zhao
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  4. Sheng Ma
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  5. Xinghui Si
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  6. Liping Liu
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  7. Ruirui Qiao
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  8. Wantong Song
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  9. Xuesi Chen
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Correspondence to Wantong Song or Xuesi Chen.

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Conflict of interest The authors declare no conflict of interest.

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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.

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Gao, Y., Zhao, H., Zhao, J. et al. Polymer-based synthetic oncolytic virus-like nanoparticles for cancer immunotherapy. Sci. China Chem. 66, 3576–3586 (2023). https://doi.org/10.1007/s11426-023-1841-8

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  • DOI: https://doi.org/10.1007/s11426-023-1841-8

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