SpringerLink
Log in

Synergistic anti-tumor therapy by a homotypic cell membrane-cloaked biomimetic nanocarrier with exceptionally potent activity against hepatic carcinoma

  • Research Article
  • Published:
Nano Research Aims and scope Submit manuscript

Abstract

Hepatic carcinoma (HC) is the sixth most frequently occurring malignancies and the third leading cause of cancer death worldwide. Sepantronium bromide (YM155) is a small molecule inhibitor of survivin, which has broad-spectrum anticancer therapeutic effects in various xenograft models. However, several-day continuous infusion is required to achieve greater antitumor efficacy because of rapid elimination from the blood circulation. Herein, a SMMC-7721 cancerous cyto-membrane-cloaked drug delivery system (DDS) (named as iM7721@GQD-YM), was developed for co-encapsulation of YM155 and graphene quantum dots (GQDs). Cytomembrane coating endowed iM7721@GQD-YM with effective targeting for homologous HC cells, excellent biocompatibility and favorable immunocompatibility for in vivo application. Surface decoration of iRGD peptide further enhanced its tumor targeting activity by iRGD-integrin recognition. In addition, under the irradiation of near-infrared ray (NIR), GQDs can directly kill tumors through photothermal effect and cause cell membrane rupture, accurately releasing YM155 at tumor sites. The physicochemical properties, in vivo and ex vivo anti-tumor efficacy, and mechanisms of iM7721@GQD-YM nanoparticles (NPs) were systematically investigated in this work. The experimental results clearly indicate that the versatile biomimetic DDS holds great potential for the treatment of HC, which merits further investigation in both pre-clinical and clinical studies.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Germany)

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Sung, H.; Ferlay, J.; Siegel, R. L.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2021, 71, 209–249.

    Article  Google Scholar 

  2. McGlynn, K. A.; Petrick, J. L.; El-Serag, H. B. Epidemiology of hepatocellular carcinoma. Hepatology 2021, 73 Suppl 1, 4–13.

    Article  CAS  Google Scholar 

  3. Anwanwan, D.; Singh, S. K.; Singh, S.; Saikam, V.; Singh, R. Challenges in liver cancer and possible treatment approaches. Biochim. Biophys. Acta Rev. Cancer 2020, 1873, 188314.

    Article  CAS  Google Scholar 

  4. Lee, Y. T.; Wang, J. J.; Luu, M.; Noureddin, M.; Kosari, K.; Agopian, V. G.; Rich, N. E.; Lu, S. C.; Tseng, H. R.; Nissen, N. N. et al. The mortality and overall survival trends of primary liver cancer in the United States. J. Natl. Cancer Inst. 2021, 113, 1531–1541.

    Article  Google Scholar 

  5. Siegel, R. L.; Miller, K. D.; Fuchs, H. E.; Jemal, A. Cancer statistics, 2021. CA Cancer J. Clin. 2021, 71, 7–33.

    Article  Google Scholar 

  6. Martínez-García, D.; Manero-Rupérez, N.; Quesada, R.; Korrodi-Gregório, L.; Soto-Cerrato, V. Therapeutic strategies involving survivin inhibition in cancer. Med. Res. Rev. 2019, 39, 887–909.

    Article  Google Scholar 

  7. Jiang, X. Y.; Wilford, C.; Duensing, S.; Munger, K.; Jones, G.; Jones, D. Participation of survivin in mitotic and apoptotic activities of normal and tumor-derived cells. J. Cell. Biochem. 2001, 83, 342–354.

    Article  CAS  Google Scholar 

  8. Min, L. H.; Ji, Y.; Bakiri, L.; Qiu, Z. X.; Cen, J.; Chen, X. T.; Chen, L. L.; Scheuch, H.; Zheng, H.; Qin, L. X. et al. Liver cancer initiation is controlled by AP-1 through SIRT6-dependent inhibition of survivin. Nat. Cell Biol. 2012, 14, 1203–1211.

    Article  CAS  Google Scholar 

  9. Su, C. Q. Survivin in survival of hepatocellular carcinoma. Cancer Lett. 2016, 379, 184–190.

    Article  CAS  Google Scholar 

  10. Santarelli, A.; Mascitti, M.; Lo Russo, L.; Sartini, D.; Troiano, G.; Emanuelli, M.; Lo, M. L. Survivin-based treatment strategies for squamous cell carcinoma. Int. J. Mol. Sci. 2018, 19, 971.

    Article  Google Scholar 

  11. Sumi, T.; Hirai, S.; Yamaguchi, M.; Tanaka, Y.; Tada, M.; Yamada, G.; Hasegawa, T.; Miyagi, Y.; Niki, T.; Watanabe, A. et al. Survivin knockdown induces senescence in TTF-1-expressing, KRAS-mutant lung adenocarcinomas. Int. J. Oncol. 2018, 53, 33–46.

    CAS  Google Scholar 

  12. Gundamaraju, R.; Vemuri, R.; Chong, W. C.; Myers, S.; Norouzi, S.; Shastri, M. D.; Eri, R. Interplay between endoplasmic reticular stress and survivin in colonic epithelial cells. Cells 2018, 7, 171.

    Article  CAS  Google Scholar 

  13. Nyquist, M. D.; Corella, A.; Burns, J.; Coleman, I.; Gao, S.; Tharakan, R.; Riggan, L.; Cai, C. M.; Corey, E.; Nelson, P. S. et al. Exploiting AR-regulated drug transport to induce sensitivity to the survivin inhibitor YM155. Mol. Cancer Res. 2017, 15, 521–531.

    Article  CAS  Google Scholar 

  14. Nakahara, T.; Kita, A.; Yamanaka, K.; Mori, M.; Amino, N.; Takeuchi, M.; Tominaga, F.; Kinoyama, I.; Matsuhisa, A.; Kudou, M. et al. Broad spectrum and potent antitumor activities of YM155, a novel small-molecule Survivin suppressant, in a wide variety of human cancer cell lines and xenograft models. Cancer Sci. 2011, 102, 614–621.

    Article  CAS  Google Scholar 

  15. Nakahara, T.; Takeuchi, M.; Kinoyama, I.; Minematsu, T.; Shirasuna, K.; Matsuhisa, A.; Kita, A.; Tominaga, F.; Yamanaka, K.; Kudoh, M. et al. YM155, a novel small-molecule survivin suppressant, induces regression of established human hormone-refractory prostate tumor xenografts. Cancer Res. 2007, 67, 8014–8021.

    Article  CAS  Google Scholar 

  16. Wang, C. L.; Zhang, W.; He, Y. J.; Gao, Z. R.; Liu, L. Y.; Yu, S. Y.; Hu, Y. X.; Wang, S.; Zhao, C. C.; Li, H. et al. Ferritin-based targeted delivery of arsenic to diverse leukaemia types confers strong anti-leukaemia therapeutic effects. Nat. Nanotechnol. 2021, 16, 1413–1423.

    Article  Google Scholar 

  17. Bao, W. E.; Liu, M.; Meng, J. Q.; Liu, S. Y.; Wang, S.; Jia, R. R.; Wang, Y. G.; Ma, G. H.; Wei, W.; Tian, Z. Y. MOFs-based nanoagent enables dual mitochondrial damage in synergistic antitumor therapy via oxidative stress and calcium overload. Nat. Commun. 2021, 12, 6399.

    Article  CAS  Google Scholar 

  18. Feng, S. N.; Ren, Y. J.; Li, H.; Tang, Y. F.; Yan, J. Y.; Shen, Z. Y.; Zhang, H. J.; Chen, F. X. Cancer cell-membrane biomimetic boron nitride nanospheres for targeted cancer therapy. Int. J. Nanomedicine 2021, 16, 2123–2136.

    Article  Google Scholar 

  19. Wang, C.; Jiang, Y.; Ma, J. M.; Wu, H. X.; Wacker, D.; Katritch, V.; Han, G. W.; Liu, W.; Huang, X. P.; Vardy, E. et al. Structural basis for molecular recognition at serotonin receptors. Science 2013, 340, 610–614.

    Article  CAS  Google Scholar 

  20. Li, H. F.; **, H.; Wan, W.; Wu, C.; Wei, L. X. Cancer nanomedicine: Mechanisms, obstacles and strategies. Nanomedicine (Lond) 2018, 13, 1639–1656.

    Article  Google Scholar 

  21. Yang, Y. Y.; Yu, Y. J.; Chen, H.; Meng, X. X.; Ma, W.; Yu, M.; Li, Z. Y.; Li, C. H.; Liu, H. L.; Zhang, X. D. et al. Illuminating platinum transportation while maximizing therapeutic efficacy by gold nanoclusters via simultaneous near-infrared-I/II imaging and glutathione scavenging. ACS Nano 2020, 14, 13536–13547.

    Article  CAS  Google Scholar 

  22. Zhong, W. H.; Zhang, X. Y.; Zeng, Y. X.; Lin, D. J.; Wu, J. Recent applications and strategies in nanotechnology for lung diseases. Nano Res. 2021, 14, 2067–2089.

    Article  CAS  Google Scholar 

  23. Sun, H. P.; Su, J. H.; Meng, Q. S.; Yin, Q.; Chen, L. L.; Gu, W. W.; Zhang, P. C.; Zhang, Z. W.; Yu, H. J.; Wang, S. L. et al. Cancer-cell-biomimetic nanoparticles for targeted therapy of homotypic tumors. Adv. Mater. 2016, 28, 9581–9588.

    Article  CAS  Google Scholar 

  24. Hu, C. M. J.; Fang, R. H.; Wang, K. C.; Luk, B. T.; Thamphiwatana, S.; Dehaini, D.; Nguyen, P.; Angsantikul, P.; Wen, C. H.; Kroll, A. V. et al. Nanoparticle biointerfacing by platelet membrane cloaking. Nature 2015, 526, 118–121.

    Article  CAS  Google Scholar 

  25. Gong, H.; Zhang, Q. Z.; Komarla, A.; Wang, S. Y.; Duan, Y. O.; Zhou, Z. D.; Chen, F.; Fang, R. H.; Xu, S.; Gao, W. W. et al. Nanomaterial biointerfacing via mitochondrial membrane coating for targeted detoxification and molecular detection. Nano Lett. 2021, 21, 2603–2609.

    Article  CAS  Google Scholar 

  26. Fan, Z. Y.; Li, P. Y.; Deng, J. J.; Bady, S. C.; Cheng, H. Cell membrane coating for reducing nanoparticle-induced inflammatory responses to scaffold constructs. Nano Res. 2018, 11, 5573–5583.

    Article  CAS  Google Scholar 

  27. Zhu, J. Y.; Zheng, D. W.; Zhang, M. K.; Yu, W. Y.; Qiu, W. X.; Hu, J. J.; Feng, J.; Zhang, X. Z. Preferential cancer cell self-recognition and tumor self-targeting by coating nanoparticles with homotypic cancer cell membranes. Nano Lett. 2016, 16, 5895–5901.

    Article  CAS  Google Scholar 

  28. Chai, Z. L.; Ran, D. N.; Lu, L. W.; Zhan, C. Y.; Ruan, H. T.; Hu, X. F.; **e, C.; Jiang, K.; Li, J. Y.; Zhou, J. F. et al. Ligand-modified cell membrane enables the targeted delivery of drug nanocrystals to glioma. ACS Nano 2019, 13, 5591–5601.

    Article  CAS  Google Scholar 

  29. Liu, W.; Ruan, M. L.; Wang, Y. M.; Song, R. G.; Ji, X.; Xu, J. K.; Dai, J.; Xue, W. Light-triggered biomimetic nanoerythrocyte for tumor-targeted lung metastatic combination therapy of malignant melanoma. Small 2018, 14, e1801754.

    Article  Google Scholar 

  30. Liu, X. J.; Sun, Y. X.; Xu, S. S.; Gao, X. N.; Kong, F. P.; Xu, K. H.; Tang, B. Homotypic cell membrane-cloaked biomimetic nanocarrier for the targeted chemotherapy of hepatocellular carcinoma. Theranostics 2019, 9, 5828–5838.

    Article  CAS  Google Scholar 

  31. Luo, Z. Q.; Weiss, D. E.; Liu, Q. Y.; Tian, B. Z. Biomimetic approaches toward smart bio-hybrid systems. Nano Res. 2018, 11, 3009–3030.

    Article  CAS  Google Scholar 

  32. Gao, J. B.; Wang, F.; Wang, S. H.; Liu, L.; Liu, K.; Ye, Y. C.; Wang, Z.; Wang, H.; Chen, B.; Jiang, J. M. et al. Hyperthermia-triggered on-demand biomimetic nanocarriers for synergetic photothermal and chemotherapy. Adv. Sci. (Weinh.) 2020, 7, 1903642.

    CAS  Google Scholar 

  33. Obaid, G.; Samkoe, K.; Tichauer, K.; Bano, S.; Park, Y.; Silber, Z.; Hodge, S.; Callaghan, S.; Guirguis, M.; Mallidi, S. et al. Is tumor cell specificity distinct from tumor selectivity in vivo?: A quantitative NIR molecular imaging analysis of nanoliposome targeting. Nano Res. 2021, 14, 1344–1354.

    Article  CAS  Google Scholar 

  34. Geng, B. J.; Shen, W. W.; Fang, F. L.; Qin, H.; Li, P.; Wang, X. L.; Li, X. K.; Pan, D. Y.; Shen, L. X. Enriched graphitic N dopants of carbon dots as F cores mediate photothermal conversion in the NIR-II window with high efficiency. Carbon 2020, 162, 220–233.

    Article  CAS  Google Scholar 

  35. Ren, Y. J.; Miao, C. L.; Tang, L.; Liu, Y. X.; Ni, P. Y.; Gong, Y.; Li, H.; Chen, F. X.; Feng, S. N. Homotypic cancer cell membranes camouflaged nanoparticles for targeting drug delivery and enhanced chemo-photothermal therapy of glioma. Pharmaceuticals (Basel) 2022, 15, 157.

    Article  CAS  Google Scholar 

  36. Li, H. F.; Wu, C.; **a, M.; Zhao, H.; Zhao, M. X.; Hou, J.; Li, R.; Wei, L. X.; Zhang, L. Targeted and controlled drug delivery using a temperature and ultra-violet responsive liposome with excellent breast cancer suppressing ability. RSC Adv. 2015, 5, 27630–27639.

    Article  CAS  Google Scholar 

  37. Bhagat, M.; Sofou, S. Membrane heterogeneities and fusogenicity in phosphatidylcholine-phosphatidic acid rigid vesicles as a function of pH and lipid chain mismatch. Langmuir 2010, 26, 1666–1673.

    Article  CAS  Google Scholar 

  38. Kanehisa, M. I.; Tsong, T. Y. Cluster model of lipid phase transitions with application to passive permeation of molecules and structure relaxations in lipid bilayers. J. Am. Chem. Soc. 1978, 100, 424–432.

    Article  CAS  Google Scholar 

  39. Sung, S. Y.; Su, Y. L.; Cheng, W.; Hu, P. F.; Chiang, C. S.; Chen, W. T.; Hu, S. H. Graphene quantum dots-mediated theranostic penetrative delivery of drug and photolytics in deep tumors by targeted biomimetic nanosponges. Nano Lett. 2019, 19, 69–81.

    Article  CAS  Google Scholar 

  40. Zhang, L. J.; Zhang, X.; Lu, G. H.; Li, F.; Bao, W. E.; Song, C.; Wei, W.; Ma, G. H. Cell membrane camouflaged hydrophobic drug nanoflake sandwiched with photosensitizer for orchestration of chemo-photothermal combination therapy. Small 2019, 15, e1805544.

    Article  Google Scholar 

  41. Chen, G.; Yang, Y. Y.; Xu, Q.; Ling, M. J.; Lin, H. M.; Ma, W.; Sun, R.; Xu, Y. C.; Liu, X. Q.; Li, N. et al. Self-amplification of tumor oxidative stress with degradable metallic complexes for synergistic cascade tumor therapy. Nano Lett. 2020, 20, 8141–8150.

    Article  CAS  Google Scholar 

  42. Hao, H. S.; Chen, Y.; Wu, M. Y. Biomimetic nanomedicine toward personalized disease theranostics. Nano Res. 2021, 8, 2491–2511.

    Article  Google Scholar 

  43. Jiang, Y.; Krishnan, N.; Zhou, J. R.; Chekuri, S.; Wei, X. L.; Kroll, A. V.; Yu, C. L.; Duan, Y. O.; Gao, W. W.; Fang, R. H. et al. Engineered cell-membrane-coated nanoparticles directly present tumor antigens to promote anticancer immunity. Adv. Mater. 2020, 32, e2001808.

    Article  Google Scholar 

  44. Liu, M. T.; Ma, W. J.; Zhao, D.; Li, J. J.; Li, Q. R.; Liu, Y. H.; Hao, L. Y.; Lin, Y. F. Enhanced penetrability of a tetrahedral framework nucleic acid by modification with iRGD for DOX-targeted delivery to triple-negative breast cancer. ACS Appl. Mater. Interfaces 2021, 13, 25825–25835.

    Article  CAS  Google Scholar 

  45. Gholizadeh, S.; Dolman, E. M.; Wieriks, R.; Sparidans, R. W.; Hennink, W. E.; Kok, R. J. Anti-GD2 immunoliposomes for targeted delivery of the survivin inhibitor sepantronium bromide (YM155) to neuroblastoma tumor cells. Pharm. Res. 2018, 35, 85.

    Article  Google Scholar 

  46. Schmitt, E.; Gehrmann, M.; Brunet, M.; Multhoff, G.; Garrido, C. Intracellular and extracellular functions of heat shock proteins: Repercussions in cancer therapy. J. Leukoc. Biol. 2007, 81, 15–27.

    Article  CAS  Google Scholar 

  47. Duan, X. P.; Chan, C.; Lin, W. B. Nanoparticle-mediated immunogenic cell death enables and potentiates cancer immunotherapy. Angew. Chem., Int. Ed. 2019, 58, 670–680.

    Article  CAS  Google Scholar 

  48. Gupta, G.; Borglum, K.; Chen, H. X. Immunogenic cell death: A step ahead of autophagy in cancer therapy. J. Cancer Immunol. (Wilmington) 2021, 3, 47–59.

    Google Scholar 

  49. Evans, S. S.; Repasky, E. A.; Fisher, D. T. Fever and the thermal regulation of immunity: The immune system feels the heat. Nat. Rev. Immunol. 2015, 15, 335–349.

    Article  CAS  Google Scholar 

  50. Geng, B. J.; Shen, W. W.; Li, P.; Fang, F. L.; Qin, H.; Li, X. K.; Pan, D. Y.; Shen, L. X. Carbon dot-passivated black phosphorus nanosheet hybrids for synergistic cancer therapy in the NIR-II window. ACS Appl. Mater. Interfaces 2019, 11, 44949–44960.

    Article  CAS  Google Scholar 

  51. Chen, H. L.; Zheng, D. H.; Pan, W. Z.; Li, X.; Lv, B.; Gu, W. X.; Machuki, J. O.; Chen, J. H.; Liang, W. Q.; Qin, K. et al. Biomimetic nanotheranostics camouflaged with cancer cell membranes integrating persistent oxygen supply and homotypic targeting for hypoxic tumor elimination. ACS Appl. Mater. Interfaces 2021, 13, 19710–19725.

    Article  CAS  Google Scholar 

  52. Gao, W. W.; Hu, C. M. J.; Fang, R. H.; Luk, B. T.; Su, J.; Zhang, L. F. Surface functionalization of gold nanoparticles with red blood cell membranes. Adv. Mater. 2013, 25, 3549–3553.

    Article  CAS  Google Scholar 

  53. Dolman, M. E. M.; den Hartog, I. J. M.; Molenaar, J. J.; Schellens, J. H. M.; Beijnen, J. H.; Sparidans, R. W. Liquid chromatography-tandem mass spectrometric assay for the light sensitive Survivin suppressant sepantronium bromide (YM155) in mouse plasma. J. Pharm. Biomed. Anal. 2014, 92, 144–148.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This work was sponsored by “One Belt One Road” International Cooperation Project of Shanghai Municipal Committee of Science and Technology (No. 19410740900), the National Natural Science Foundation of China (No. 52002239), the International Science and Technology Cooperation Programme of Ministry of Science and Technology of China (No. 2019YFE0116800), and Natural Science Foundation of Shanghai (No. 21ZR1422800).

Author information

Author notes

  1. Shini Feng and Pinyue Ni contributed equally to this work.

Authors and Affiliations

  1. School of Lifesciences, Shanghai University, Shanghai, 200444, China

    Shini Feng, Pinyue Ni, Yan Gong, Hui Li, Chenlin Miao, Ruyu Fan, Levon Galstyan, Fuxue Chen & Huafei Li

  2. School of Environmental and Chemical Engineering, Shanghai University, Shanghai, 200444, China

    Bijiang Geng & Dengyu Pan

  3. SLAVMED Medical Center, Manandyan st., 9 bld., Yerevan, 0037, Republic of Armenia

    Levon Galstyan

Authors
  1. Shini Feng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Pinyue Ni
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yan Gong
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Bijiang Geng
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hui Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Chenlin Miao
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ruyu Fan
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Levon Galstyan
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Dengyu Pan
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Fuxue Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Huafei Li
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Fuxue Chen or Huafei Li.

Electronic Supplementary Material

12274_2022_4462_MOESM1_ESM.pdf

Synergistic anti-tumor therapy by a homotypic cell membranecloaked biomimetic nanocarrier with exceptionally potent activity against hepatic carcinoma

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Feng, S., Ni, P., Gong, Y. et al. Synergistic anti-tumor therapy by a homotypic cell membrane-cloaked biomimetic nanocarrier with exceptionally potent activity against hepatic carcinoma. Nano Res. 15, 8255–8269 (2022). https://doi.org/10.1007/s12274-022-4462-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12274-022-4462-8

Keywords

Search

Navigation