Skip to main content
SpringerLink
Log in

Light-activated nitric-oxide overproduction theranostic nanoplatform based on long-circulating biomimetic nanoerythrocyte for enhanced cancer gas therapy

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

Abstract

The limited intratumoral perfusion of nitric oxide (NO)-carrying nanoparticles into solid tumors caused by the inherent biological barriers in vivo greatly attenuates their generated efficacy. Herein, through entrapping heat-sensitive NO donors (BNN6) on mesoporous polydopamine nanoparticles (M-PDA) and subsequently enveloping with red blood cells membranes, a heat-responsive biomimetic theranostic nanoerythrocyte (M/B@R) is developed to boost NO-based cancer therapy. The reserved intact structure of red blood cells membranes (RBCm) endows M/B@R with superior biosafety and stealth properties for prolonged circulation time and subsequent enhanced tumor accumulation. Once internalized in tumors and excited by near-infrared light (NIR, 808 nm) irradiation, M/B@R can not only yield plenty of heat for photothermal therapy (PTT) but also achieve the overproduction of NO for highly-efficient NO gas therapy due to its high loading capacity and NIR-absorbing property of M-PDA. The generated NO further ensures the formation of ONOO− which possesses remarkable toxicity to tumor as well as alleviating tumor hypoxia. It is found that M/B@R with NIR as the excitation source can significantly induce synthetic lethality to tumors via the hyperthermia, DNA damage and the ease of tumor hypoxia. Simultaneously, M/B@R also exhibits the potential for bimodal fluorescence and photothermal imaging. The RBCm-camouflaged NO delivery nanoplatform with bimodal imaging capability in this work may provide a new combinatorial paradigm to induce PTT/NO for cancer theranostic applications.

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. Du Z, Zhang X, Guo Z, Xie J, Dong X, Zhu S, Du J, Gu Z, Zhao Y. Adv Mater, 2018, 30: 1804046

    Article  Google Scholar 

  2. Ma Z, Liu S, Ke Y, Wang H, Chen R, Xiang Z, Xie Z, Shi Q, Yin J. Biomaterials, 2020, 255: 120141

    Article  CAS  PubMed  Google Scholar 

  3. Sung YC, Jin PR, Chu LA, Hsu FF, Wang MR, Chang CC, Chiou SJ, Qiu JT, Gao DY, Lin CC, Chen YS, Hsu YC, Wang J, Wang FN, Yu PL, Chiang AS, Wu AYT, Ko JJS, Lai CPK, Lu TT, Chen Y. Nat Nanotechnol, 2019, 14: 1160–1169

    Article  CAS  PubMed  Google Scholar 

  4. Zhao P, Jin Z, Chen Q, Yang T, Chen D, Meng J, Lu X, Gu Z, He Q. Nat Commun, 2018, 9: 4241

    Article  PubMed  PubMed Central  Google Scholar 

  5. Wu D, Duan X, Guan Q, Liu J, Yang X, Zhang F, Huang P, Shen J, Shuai X, Cao Z. Adv Funct Mater, 2019, 29: 1900095

    Article  Google Scholar 

  6. Jin Z, Wen Y, Xiong L, Yang T, Zhao P, Tan L, Wang T, Qian Z, Su BL, He Q. Chem Commun, 2017, 53: 5557–5560

    Article  CAS  Google Scholar 

  7. An L, Wang X, Rui X, Lin J, Yang H, Tian Q, Tao C, Yang S. Angew Chem Int Ed, 2018, 57: 15782–15786

    Article  CAS  Google Scholar 

  8. Basudhar D, Ridnour LA, Cheng R, Kesarwala AH, Heinecke J, Wink DA. Coord Chem Rev, 2016, 306: 708–723

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Thomas DD, Ridnour LA, Isenberg JS, Flores-Santana W, Switzer CH, Donzelli S, Hussain P, Vecoli C, Paolocci N, Ambs S, Colton CA, Harris CC, Roberts DD, Wink DA. Free Radical Biol Med, 2008, 45: 18–31

    Article  CAS  Google Scholar 

  10. Seabra AB, de Lima R, Calderón M. Curr Top Med Chem, 2015, 15: 298–308

    Article  CAS  PubMed  Google Scholar 

  11. Carpenter AW, Schoenfisch MH. Chem Soc Rev, 2012, 41: 3742–3752

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Yu S, Li G, Liu R, Ma D, Xue W. Adv Funct Mater, 2018, 28: 1707440

    Article  Google Scholar 

  13. Huang Z, Fu J, Zhang Y. J Med Chem, 2017, 60: 7617–7635

    Article  CAS  PubMed  Google Scholar 

  14. Fan W, Yung BC, Chen X. Angew Chem Int Ed, 2018, 57: 8383–8394

    Article  CAS  Google Scholar 

  15. Seabra AB, Justo GZ, Haddad PS. Biotech Adv, 2015, 33: 1370–1379

    Article  CAS  Google Scholar 

  16. Wink DA, Vodovotz Y, Laval J, Laval F, Dewhirst MW, Mitchell JB. Carcinogenesis, 1998, 19: 711–721

    Article  CAS  PubMed  Google Scholar 

  17. Kim J, Yung BC, Kim WJ, Chen X. J Control Release, 2017, 263: 223–230

    Article  CAS  PubMed  Google Scholar 

  18. Guo R, Tian Y, Wang Y, Yang W. Adv Funct Mater, 2017, 27: 1606398

    Article  Google Scholar 

  19. Wan SS, Zeng JY, Cheng H, Zhang XZ. Biomaterials, 2018, 185: 51–62

    Article  CAS  PubMed  Google Scholar 

  20. Deng Y, Jia F, Chen S, Shen Z, Jin Q, Fu G, Ji J. Biomaterials, 2018, 187: 55–65

    Article  CAS  PubMed  Google Scholar 

  21. Gehring J, Trepka B, Klinkenberg N, Bronner H, Schleheck D, Polarz S. J Am Chem Soc, 2016, 138: 3076–3084

    Article  CAS  PubMed  Google Scholar 

  22. Wang PG, Xian M, Tang X, Wu X, Wen Z, Cai T, Janczuk AJ. Chem Rev, 2002, 102: 1091–1134

    Article  CAS  PubMed  Google Scholar 

  23. Hu Y, Lv T, Ma Y, Xu J, Zhang Y, Hou Y, Huang Z, Ding Y. Nano Lett, 2019, 19: 2731–2738

    Article  CAS  PubMed  Google Scholar 

  24. Li M, Li J, Chen J, Liu Y, Cheng X, Yang F, Gu N. ACS Nano, 2020, 14: 2024–2035

    Article  CAS  PubMed  Google Scholar 

  25. Ho CM, Liao KJ, Lok CN, Che CM. Chem Commun, 2011, 47: 10776–10778

    Article  CAS  Google Scholar 

  26. Fan W, Bu W, Zhang Z, Shen B, Zhang H, He Q, Ni D, Cui Z, Zhao K, Bu J, Du J, Liu J, Shi J. Angew Chem Int Ed, 2015, 54: 14026–14030

    Article  CAS  Google Scholar 

  27. Zhang K, Xu H, Jia X, Chen Y, Ma M, Sun L, Chen H. ACS Nano, 2016, 10: 10816–10828

    Article  CAS  PubMed  Google Scholar 

  28. Gao Q, Zhang X, Yin W, Ma D, Xie C, Zheng L, Dong X, Mei L, Yu J, Wang C, Gu Z, Zhao Y. Small, 2018, 14: 1802290

    Article  Google Scholar 

  29. Jin Z, Wen Y, Hu Y, Chen W, Zheng X, Guo W, Wang T, Qian Z, Su BL, He Q. Nanoscale, 2017, 9: 3637–3645

    Article  CAS  PubMed  Google Scholar 

  30. Xiang HJ, Deng Q, An L, Guo M, Yang SP, Liu JG. Chem Commun, 2016, 52: 148–151

    Article  CAS  Google Scholar 

  31. Zhang X, Tian G, Yin W, Wang L, Zheng X, Yan L, Li J, Su H, Chen C, Gu Z, Zhao Y. Adv Funct Mater, 2015, 25: 3049–3056

    Article  CAS  Google Scholar 

  32. Xu Y, Ren H, Liu J, Wang Y, Meng Z, He Z, Miao W, Chen G, Li X. Nanoscale, 2019, 11: 5474–5488

    Article  CAS  PubMed  Google Scholar 

  33. Hu D, Liu C, Song L, Cui H, Gao G, Liu P, Sheng Z, Cai L. Nanoscale, 2016, 8: 17150–17158

    Article  CAS  PubMed  Google Scholar 

  34. Dong Z, Feng L, Hao Y, Chen M, Gao M, Chao Y, Zhao H, Zhu W, Liu J, Liang C, Zhang Q, Liu Z. J Am Chem Soc, 2018, 140: 2165–2178

    Article  CAS  PubMed  Google Scholar 

  35. Rong L, Zhang Y, Li WS, Su Z, Fadhil JI, Zhang C. Biomaterials, 2019, 225: 119515

    Article  CAS  PubMed  Google Scholar 

  36. Xing Y, Zhang J, Chen F, Liu J, Cai K. Nanoscale, 2017, 9: 8781–8790

    Article  CAS  PubMed  Google Scholar 

  37. Liu W, Ruan M, Wang Y, Song R, Ji X, Xu J, Dai J, Xue W. Small, 2018, 14: 1801754

    Article  Google Scholar 

  38. Ji X, Ma Y, Liu W, Liu L, Yang H, Wu J, Zong X, Dai J, Xue W. ACS Nano, 2020, 14: 7462–7474

    Article  CAS  PubMed  Google Scholar 

  39. Hu CMJ, Zhang L, Aryal S, Cheung C, Fang RH, Zhang L. Proc Natl Acad Sci USA, 2011, 108: 10980–10985

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Fang RH, Kroll AV, Gao W, Zhang L. Adv Mater, 2018, 30: 1706759

    Article  Google Scholar 

  41. Wu W, Yu L, Pu Y, Yao H, Chen Y, Shi J. Adv Mater, 2020, 32: 2000542

    Article  CAS  Google Scholar 

  42. Zhang L, Wu C, Mu S, Xue W, Ma D. Colloids Surfs B-Biointerfaces, 2019, 181: 902–909

    Article  CAS  Google Scholar 

  43. Beckman JS. Ann New York Acad Sci, 2006, 738: 69–75

    Article  Google Scholar 

  44. Beckman JS, Beckman TW, Chen J, Marshall PA, Freeman BA. Proc Natl Acad Sci USA, 1990, 87: 1620–1624

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Irwin C, Roberts W, Irwin C, Roberts W, Naseem KM. Platelets, 2009, 20: 478–486

    Article  CAS  PubMed  Google Scholar 

  46. Chen F, Xing Y, Wang Z, Zheng X, Zhang J, Cai K. Langmuir, 2016, 32: 12119–12128

    Article  CAS  PubMed  Google Scholar 

  47. Guan BY, Yu L, Lou XWD. J Am Chem Soc, 2016, 138: 11306–11311

    Article  CAS  PubMed  Google Scholar 

  48. Fan J, He N, He Q, Liu Y, Ma Y, Fu X, Liu Y, Huang P, Chen X. Nanoscale, 2015, 7: 20055–20062

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Obregón S, Ruíz-Gómez MA, Hernández-Uresti DB. J Colloid Interface Sci, 2017, 506: 111–119

    Article  PubMed  Google Scholar 

  50. Wang D, Niu L, Qiao ZY, Cheng DB, Wang J, Zhong Y, Bai F, Wang H, Fan H. ACS Nano, 2018, 12: 3796–3803

    Article  CAS  PubMed  Google Scholar 

  51. Liu H, Zhu X, Guo H, Huang H, Huang S, Huang S, Xue W, Zhu P, Guo R. Appl Mater Today, 2020, 20: 100781

    Article  Google Scholar 

  52. Wang C, Ye Y, Sun W, Yu J, Wang J, Lawrence DS, Buse JB, Gu Z. AdvMater, 2017, 29: 1606617

    Google Scholar 

  53. Wu Z, Esteban-Fernández de Ávila B, Martín A, Christianson C, Gao W, Thamphiwatana SK, Escarpa A, He Q, Zhang L, Wang J. Nanoscale, 2015, 7: 13680–13686

    Article  CAS  PubMed  Google Scholar 

  54. Jaiswal S, Jamieson CHM, Pang WW, Park CY, Chao MP, Majeti R, Traver D, van Rooijen N, Weissman IL. Cell, 2009, 138: 271–285

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Sun M, Yang D, Wang C, Bi H, Zhou Y, Wang X, Xu J, He F, Gai S, Yang P. Biomater Sci, 2019, 7: 4769–4781

    Article  CAS  PubMed  Google Scholar 

  56. Ren W, Yan Y, Zeng L, Shi Z, Gong A, Schaaf P, Wang D, Zhao J, Zou B, Yu H, Chen G, Brown EMB, Wu A. Adv Healthcare Mater, 2015, 4: 1526–1536

    Article  CAS  Google Scholar 

  57. Zhang SQ, Liu X, Sun QX, Johnson O, Yang T, Chen ML, Wang JH, Chen W. J Mater Chem B, 2020, 8: 1396–1404

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Du X, Qiu J, Deng S, Du Z, Cheng X, Wang H. ACS Sustain Chem Eng, 2020, 8: 5799–5806

    Article  CAS  Google Scholar 

  59. Liu S, Cai X, Xue W, Ma D, Zhang W. Carbohydrate Polyms, 2020, 234: 115928

    Article  CAS  Google Scholar 

  60. Tian G, Zheng X, Zhang X, Yin W, Yu J, Wang D, Zhang Z, Yang X, Gu Z, Zhao Y. Biomaterials, 2015, 40: 107–116

    Article  CAS  PubMed  Google Scholar 

  61. Zhang Z, Tan S, Feng SS. Biomaterials, 2012, 33: 4889–4906

    Article  CAS  PubMed  Google Scholar 

  62. Nguyen SC, Zhang Q, Manthiram K, Ye X, Lomont JP, Harris CB, Weller H, Alivisatos AP. ACS Nano, 2016, 10: 2144–2151

    Article  CAS  PubMed  Google Scholar 

  63. Rao L, Bu LL, Xu JH, Cai B, Yu GT, Yu X, He Z, Huang Q, Li A, Guo SS, Zhang WF, Liu W, Sun ZJ, Wang H, Wang TH, Zhao XZ. Small, 2015, 11: 6225–6236

    Article  CAS  PubMed  Google Scholar 

  64. Silveira LR, Pereira-Da-Silva L, Juel C, Hellsten Y. Free Radical Biol Med, 2003, 35: 455–464

    Article  CAS  Google Scholar 

  65. Arbogast S, Reid MB. Am J Physiol-Regulatory Integrative Comp Physiol, 2004, 287: R698–R705

    Article  CAS  Google Scholar 

  66. Zhang XG, Jin L, Tian Z, Wang J, Yang Y, Liu JF, Chen Y, Hu CH, Chen TY, Zhao YR, He YL. Cancer Sci, 2019, 110: 1054–1063

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Cheng CH, Su YL, Ma HL, Deng YQ, Feng J, Chen XL, Jie YK, Guo ZX. Chemosphere, 2020, 239: 124668

    Article  CAS  PubMed  Google Scholar 

  68. Guo YX, Zhang GM, Yao XL, Tong R, Cheng CY, Zhang TT, Wang ST, Yang H, Wang F. Theriogenology, 2019, 126: 55–62

    Article  CAS  PubMed  Google Scholar 

  69. Chen Z, Zhao P, Luo Z, Zheng M, Tian H, Gong P, Gao G, Pan H, Liu L, Ma A, Cui H, Ma Y, Cai L. ACS Nano, 2016, 10: 10049–10057

    Article  CAS  PubMed  Google Scholar 

  70. van den Tweel ERW, Nijboer C, Kavelaars A, Heijnen CJ, Groenendaal F, van Bel F. J Neuroimmunol, 2005, 167: 64–71

    Article  CAS  PubMed  Google Scholar 

  71. Rogakou EP, Pilch DR, Orr AH, Ivanova VS, Bonner WM. J Biol Chem, 1998, 273: 5858–5868

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Natural Science Foundation of China (31870943), the Thousands of Doctors (Postdoctoral) Program of Guangdong Academy of Sciences (2019GDA-SYL-0103015), the Basic and Applied Basic Research Fund of Guangdong Province (2019A1515110663), and the Traditional Chinese Medicine Bureau of Guangdong Province (20201109).

Author information

Author notes

  1. These authors contributed equally to this work.

Authors and Affiliations

  1. Guangdong Provincial Engineering and Technological Research Center for Drug Carrier Development, Department of Biomedical Engineering, Jinan University, Guangzhou, 510632, China

    Cheng-Guang Wu, Jing-Lan Liang, Xiang Wang, Xiaoyan Zhou, Meng Wang, Wen-Bo Wang, Dong Ma & Wei Xue

  2. Institute of Medicine and Health, Guangdong Academy of Sciences, National Engineering Research Center for Healthcare Devices, Guangdong Key Lab of Medical Electronic Instruments and Polymer Material Products, Guangdong Institute of Medical Instruments, Guangzhou, 510500, China

    Xiaoyan Zhou

  3. Department of Light Chemical Engineering, Guangdong Polytechnic, Foshan, 528041, China

    Xiang Cai

  4. Department of Critical Care Medicine, First Affiliated Hospital, Jinan University, Guangzhou, 510632, China

    Jun Xu

  5. MOE Key Laboratory of Tumor Molecular Biology, Jinan University, Guangzhou, 510632, China

    Dong Ma & Wei Xue

Authors
  1. Cheng-Guang Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jing-Lan Liang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xiang Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xiaoyan Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xiang Cai
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jun Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Meng Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Wen-Bo Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Dong Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Wei Xue
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Dong Ma or Wei Xue.

Additional information

Conflict of interest

The authors declare no conflict of interest.

Supporting Information

11426_2021_1045_MOESM1_ESM.pdf

Light-Activated Nitric-Oxide Overproduction Theranostic Nanoplatform Based on Long-Circulating Biomimetic Nanoerythrocyte for Enhanced Cancer Gas Therapy

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wu, CG., Liang, JL., Wang, X. et al. Light-activated nitric-oxide overproduction theranostic nanoplatform based on long-circulating biomimetic nanoerythrocyte for enhanced cancer gas therapy. Sci. China Chem. 64, 1796–1810 (2021). https://doi.org/10.1007/s11426-021-1045-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11426-021-1045-9

Search

Navigation