Skip to main content
SpringerLink
Log in

A triple-combination nanotechnology platform based on multifunctional RNA hydrogel for lung cancer therapy

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

Abstract

Conventional cancer combination therapy usually involves systemic delivery of anticancer drugs which may lead to the destruction of normal cells and physiological toxicity due to the lack of targeting ability and toxicity of drug carriers. In the present study, a triple combination nanosystem of gene therapy, chemotherapy and phototherapy delivered by multifunctional RNA nanohydrogels (RNA NHs) was established. By taking the advantages of DNA nanotechnology and rolling circle transcription (RCT), three lung cancer inhibitor microRNA (let-7a, microRNA 34a, microRNA 145) hairpins were integrated in one RNA NH nanoparticle, leading to the simultaneous silencing of three targeted mRNAs. Meanwhile, RNA NH carried doxorubicin (DOX, a chemotherapy drug) as well as 5,10,15,20-tetrakis (1-methylpyridinium-4-yl) porphyrin (TMPyP4, a photosensitizer) and delivered these drugs to cancer cells. It was demonstrated that lung cancer inhibitor microRNAs integrated in RNA NHs, DOX and TMPyP4 could play a synergistic anti-cancer role in multi-drug resistance cancer cells. Under the action of aptamer sequence S6 that was modified with cholesterol, the resulting RNA NHs were condensed to feasible size without the assistance of polyelectrolyte condensation reagents and showed cancer-specific cellular targeting. Subsequently, thousands of copies of miRNA together with chemotherapy drug as well as photosensitizer were delivered to cancer cells specifically, and an ideal synergistic treatment effect was achieved in vivo, thus playing a combined role of gene therapy, chemotherapy and phototherapy. Through this study, it can be concluded that the triple combination therapy nanosystem can overcome the multidrug resistance caused by the malfunction of genes in chemotherapy and shows a great potential in the field of multifunctional synergistic cancer 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. Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ, He J. CA-A Cancer J Clinicians, 2016, 66: 115–132

    Google Scholar 

  2. Alam SK, Astone M, Liu P, Hall SR, Coyle AM, Dankert EN, Hoffman DK, Zhang W, Kuang R, Roden AC, Mansfield AS, Hoeppner LH. Commun Biol, 2018, 1: 43

    PubMed  PubMed Central  Google Scholar 

  3. Inamura K. Cells, 2017, 6: 12

    PubMed Central  Google Scholar 

  4. Siegel RL, Miller KD, Fedewa SA, Ahnen DJ, Meester RG, Barzi A, Jemal A. Ca A Cancer J Clin, 2017, 67: 104–117

    Google Scholar 

  5. Cui H, Huan ML, Ye WL, Liu DZ, Teng ZH, Mei QB, Zhou SY. Mol Pharm, 2017, 14: 746–756

    PubMed  CAS  Google Scholar 

  6. 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

    CAS  Google Scholar 

  7. Pugazhendhi A, Edison TNJI, Velmurugan BK, Jacob JA. Karuppusamy I, 2018, 200: 26

    CAS  Google Scholar 

  8. Dua K, Hansbro NG, Foster PS, Hansbro PM. Drug Deliv Transl Res, 2016, 7: 1–11

    Google Scholar 

  9. Wei H, Zhang X, Cheng C, Cheng SX, Zhuo RX. Biomaterials, 2007, 28: 99–107

    PubMed  CAS  Google Scholar 

  10. Zhang Z, Shi L, Wu C, Su Y, Qian J, Deng H, Zhu X. ACS Appl Mater Interfaces, 2017, 9: 29505–29514

    PubMed  CAS  Google Scholar 

  11. Li C, Li H, Ge J, Jie G. Chem Commun, 2019, 55: 3919–3922

    CAS  Google Scholar 

  12. Dai X, Tan C. Adv Drug Deliver Rev, 2015, 81: 184–197

    CAS  Google Scholar 

  13. Chen J, Luo H, Liu Y, Zhang W, Li H, Luo T, Zhang K, Zhao Y, Liu J. ACS Nano, 2017, 11: 12849–12862

    PubMed  CAS  Google Scholar 

  14. Cheng Y, Cheng H, Jiang C, Qiu X, Wang K, Huan W, Yuan A, Wu J, Hu Y. Nat Commun, 2015, 6: 8785

    PubMed  PubMed Central  CAS  Google Scholar 

  15. Sun M, Qian QH, Shi LL, Xu L, Liu QF, Zhou LZ, Zhu XY, Yue JM, Yan DY. Sci China Chem, 2019, 62: 1–6

    Google Scholar 

  16. Chakraborty C, Sharma AR, Sharma G, Sarkar BK, Lee SS. Oncotarget, 2018, 9: 10164–10174

    PubMed  PubMed Central  Google Scholar 

  17. Park H, Yang J, Lee J, Haam S, Choi IH, Yoo KH. ACS Nano, 2009, 3: 2919–2926

    PubMed  CAS  Google Scholar 

  18. Guo F, Yu M, Wang J, Tan F, Li N. ACS Appl Mater Interfaces, 2015, 7: 20556–20567

    PubMed  CAS  Google Scholar 

  19. Feng L, Gao M, Tao D, Chen Q, Wang H, Dong Z, Chen M, Liu Z. Adv Funct Mater, 2016, 26: 2207–2217

    CAS  Google Scholar 

  20. Bhaskaran V, Nowicki MO, Idriss M, Jimenez MA, Lugli G, Hayes JL, Mahmoud AB, Zane RE, Passaro C, Ligon KL, Haas-Kogan D, Bronisz A, Godlewski J, Lawler SE, Chiocca EA, Peruzzi P. Nat Commun, 2019, 10: 442

    PubMed  PubMed Central  CAS  Google Scholar 

  21. Zarredar H, Pashapour S, Ansarin K, Khalili M, Baghban R, Farajnia S. J Cell Physiol, 2019, 234: 1560–1566

    PubMed  CAS  Google Scholar 

  22. Zhu N, Weng S, Wang J, Chen J, Yu L, Fang X, Yuan Y. J Cancer Res Clin Oncol, 2019, 145: 3021–3036

    PubMed  CAS  Google Scholar 

  23. Housman G, Byler S, Heerboth S, Lapinska K, Longacre M, Snyder N, Sarkar S. Cancers, 2014, 6: 1769–1792

    PubMed  PubMed Central  CAS  Google Scholar 

  24. Wu J, Zhao L, Xu X, Bertrand N, Choi WI, Yameen B, Shi J, Shah V, Mulvale M, MacLean JL, Farokhzad OC. Angew Chem Int Ed, 2015, 54: 9218–9223

    CAS  Google Scholar 

  25. Zheng M, Ruan S, Liu S, Sun T, Qu D, Zhao H, Xie Z, Gao H, Jing X, Sun Z. ACS Nano, 2015, 9: 11455–11461

    PubMed  CAS  Google Scholar 

  26. Zhu G, Mei L, Vishwasrao HD, Jacobson O, Wang Z, Liu Y, Yung BC, Fu X, Jin A, Niu G, Wang Q, Zhang F, Shroff H, Chen X. Nat Commun, 2017, 8: 1482

    PubMed  PubMed Central  Google Scholar 

  27. Zhang L, Abdullah R, Hu X, Bai H, Fan H, He L, Liang H, Zou J, Liu Y, Sun Y, Zhang X, Tan W. J Am Chem Soc, 2019, 141: 4282–4290

    PubMed  PubMed Central  CAS  Google Scholar 

  28. Guo Y, Li S, Wang Y, Zhang S. Anal Chem, 2017, 89: 2267–2274

    PubMed  CAS  Google Scholar 

  29. Lee JB, Hong J, Bonner DK, Poon Z, Hammond PT. Nat Mater, 2012, 11: 316–322

    PubMed  PubMed Central  CAS  Google Scholar 

  30. Bai J, Jia X, Zhen W, Cheng W, Jiang X. J Am Chem Soc, 2018, 140: 106–109

    PubMed  CAS  Google Scholar 

  31. Johnson CD, Esquela-Kerscher A, Stefani G, Byrom M, Kelnar K, Ovcharenko D, Wilson M, Wang X, Shelton J, Shingara J, Chin L, Brown D, Slack FJ. Cancer Res, 2007, 67: 7713–7722

    PubMed  CAS  Google Scholar 

  32. Mou J, Lin T, Huang F, Chen H, Shi J. Biomaterials, 2016, 84: 13–24

    PubMed  CAS  Google Scholar 

  33. Deng X, Cao M, Zhang J, Hu K, Yin Z, Zhou Z, Xiao X, Yang Y, Sheng W, Wu Y, Zeng Y. Biomaterials, 2014, 35: 4333–4344

    PubMed  CAS  Google Scholar 

  34. Huang L, Tao K, Liu J, Qi C, Xu L, Chang P, Gao J, Shuai X, Wang G, Wang Z, Wang L. ACS Appl Mater Interfaces, 2016, 8: 6577–6585

    PubMed  CAS  Google Scholar 

  35. Ren K, Liu Y, Wu J, Zhang Y, Zhu J, Yang M, Ju H. Nat Commun, 2016, 7: 13580

    PubMed  PubMed Central  CAS  Google Scholar 

  36. Chen Z, Zeng H, Guo Y, Liu P, Pan H, Deng A, Hu J. J Exp Clin Cancer Res, 2010, 29: 151

    PubMed  PubMed Central  Google Scholar 

  37. Kulkarni A, Natarajan SK, Chandrasekar V, Pandey PR, Sengupta S. ACS Nano, 2016, 10: 9227–9242

    PubMed  CAS  Google Scholar 

  38. Kim M, Mun H, Sung CO, Cho EJ, Jeon HJ, Chun SM, Jung DJ, Shin TH, Jeong GS, Kim DK, Choi EK, Jeong SY, Taylor AM, Jain S, Meyerson M, Jang SJ. Nat Commun, 2019, 10: 3991

    PubMed  PubMed Central  Google Scholar 

  39. Jang M, Kim JH, Nam HY, Kwon IC, Ahn HJ. Nat Commun, 2015, 6: 7930

    PubMed  PubMed Central  CAS  Google Scholar 

  40. Bagalkot V, Farokhzad OC, Langer R, Jon S. Angew Chem Int Ed, 2010, 45: 8149–8152

    Google Scholar 

  41. Daly TA, Wang M, Regen SL. Langmuir, 2011, 27: 2159–2161

    PubMed  PubMed Central  CAS  Google Scholar 

  42. Shiao YS, Chiu HH, Wu PH, Huang YF. ACS Appl Mater Interfaces, 2014, 6: 21832–21841

    PubMed  CAS  Google Scholar 

  43. Wu Y, Zhang H, Xiang J, Mao Z, Shen G, Yang F, Liu Y, Wang W, Du N, Zhang J, Tang Y. Talanta, 2018, 179: 501–506

    PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Natural Science Foundation of China (21876074, 21605071, 21775063), the Shandong Provincial Key Research and Development Program (2017CXZC1206, GG201809250462), the Shandong Provincial Natural Science Foundation Major Basic Research Project (ZR2018ZC0231) and Taishan Scholars Program of Shandong Province (tsqn201812101).

Author information

Authors and Affiliations

  1. Collaborative Innovation Center of Tumor Marker Detection Technology, Equipment and Diagnosis-Therapy Integration in Universities of Shandong, Shandong Province Key Laboratory of Detection Technology for Tumor Makers, School of Chemistry and Chemical Engineering, Linyi University, Linyi, 276005, China

    Junwei Li, Dandan Yuan, Xiangjiang Zheng, Xinyue Zhang, Xuemei Li & Shusheng Zhang

  2. College of Chemistry, Chemical Engineering and Materials Science, Cooperative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Shandong Normal University, Jinan, 250014, China

    Junwei Li & Dandan Yuan

Authors
  1. Junwei Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dandan Yuan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xiangjiang Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xinyue Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xuemei Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Shusheng Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Xuemei Li or Shusheng Zhang.

Ethics declarations

Conflict of interest The authors declare that they have no conflict of interest.

Supporting Information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, J., Yuan, D., Zheng, X. et al. A triple-combination nanotechnology platform based on multifunctional RNA hydrogel for lung cancer therapy. Sci. China Chem. 63, 546–553 (2020). https://doi.org/10.1007/s11426-019-9673-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11426-019-9673-4

Keywords

Search

Navigation