Log in

Platelet-based bioactive systems guided precision targeting and immune regulation for cancer therapy

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

Abstract

The antitumor effects of conventional drug carriers are often attenuated and limited in application by biological barriers associated with tumor heterogeneity and resistance brought about by low tumor immunogenicity. With the rapid development of nanotechnology, naturally derived bioactive materials, and live cell carriers, a promising strategy emerges for targeting the tumor microenvironment (TME) for precision cancer therapy. The unique injury-targeting properties of platelets can significantly extend functional activity, which cannot be achieved with conventional nanocarriers. In this review, three strategies based on plateletengineered materials are systematically described, namely nanoparticles for platelet membrane camouflage, engineered activated platelets, and targeted-platelets nanosystems. Platelet-based nanomaterials can effectively coordinate local and distant tumor-host crosstalk with controlled active tumor site recognition and killing effects due to the presence of specific membrane proteins on the surface and the self-secretion of a large number of particles. Further advances in platelets for effectively overcoming biological barriers and reducing immune resistance in cancer immunotherapy applications will be discussed in future clinical practice. This review provides an overview of recent research advances in platelet-based bioactive material-directed immunotherapy and chemotherapy to inform future antitumor combination therapies.

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

Access this article

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.

Similar content being viewed by others

References

  1. Blankenstein, T.; Coulie, P. G.; Gilboa, E.; Jaffee, E. M. The determinants of tumour immunogenicity. Nat. Rev. Cancer 2012, 12, 307–313.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Kost, J.; Mathiowitz, E.; Azagury, A. Advances in drug delivery and theranostics. Adv. Funct. Mater. 2021, 31, 2108838.

    Article  CAS  Google Scholar 

  3. Gong, X.; Li, J.; Tan, T.; Wang, Z. W.; Wang, H.; Wang, Y. Q.; Xu, X. X.; Zhang, Z. W.; Li, Y. P. Emerging approaches of cell-based nanosystems to target cancer metastasis. Adv. Funct. Mater. 2019, 29, 1903441.

    Article  CAS  Google Scholar 

  4. Yang, J. L.; Zhang, X. C.; Liu, C.; Wang, Z.; Deng, L. F.; Feng, C.; Tao, W.; Xu, X. Y.; Cui, W. G. Biologically modified nanoparticles as theranostic bionanomaterials. Prog. Mater. Sci. 2021, 118, 100768.

    Article  CAS  Google Scholar 

  5. Alderton, G. Synthetic bacterial cancer therapy. Science 2019, 365, 459.6–460.

    Article  Google Scholar 

  6. Finck, A. V.; Blanchard, T.; Roselle, C. P.; Golinelli, G.; June, C. H. Engineered cellular immunotherapies in cancer and beyond. Nat. Med. 2022, 28, 678–689.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. van der Meijden, P. E. J.; Heemskerk, J. W. M. Platelet biology and functions: New concepts and clinical perspectives. Nat. Rev. Cardiol. 2019, 16, 166–179.

    Article  CAS  PubMed  Google Scholar 

  8. Donisan, T.; Balanescu, D. V.; Iliescu, G.; Marmagkiolis, K.; Iliescu, C. Acute coronary syndrome, thrombocytopenia, and antiplatelet therapy in critically ill cancer patients. In Oncologic Critical Care. 2021, 1, 1-2Nates, J. L.; Price, K. J., Eds.; Springer: Cham, 2020; pp 711–732.

    Google Scholar 

  9. Menter, D. G.; Kopetz, S.; Hawk, E.; Sood, A. K.; Loree, J. M.; Gresele, P.; Honn, K. V. Platelet “first responders” in wound response, cancer, and metastasis. Cancer Metastasis Rev. 2017, 36, 199–213.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Sierko, E.; Wojtukiewicz, M. Z. Platelets and angiogenesis in malignancy. Semin. Thromb. Hemost. 2004, 30, 95–108.

    Article  CAS  PubMed  Google Scholar 

  11. Schlesinger, M. Role of platelets and platelet receptors in cancer metastasis. J. Hematol. Oncol. 2018, 11, 125.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. 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  PubMed  PubMed Central  Google Scholar 

  13. Yang, F. J.; Kong, Z. Q.; Ji, Q. Y.; Li, S. M.; Sun, J.; He, Z. G.; Zhang, S. W.; Luo, C. Platelet-inspired nanotherapeutics for biomedical applications. ACS Mater. Lett. 2023, 5, 429–449.

    Article  CAS  Google Scholar 

  14. Zhuang, J.; Gong, H.; Zhou, J. R.; Zhang, Q. Z.; Gao, W. W.; Fang, R. H.; Zhang, L. F. Targeted gene silencing in vivo by platelet membrane-coated metal-organic framework nanoparticles. Sci. Adv. 2020, 6, eaaz6108.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Bahmani, B.; Gong, H.; Luk, B. T.; Haushalter, K. J.; DeTeresa, E.; Previti, M.; Zhou, J. R.; Gao, W. W.; Bui, J. D.; Zhang, L. F. et al. Intratumoral immunotherapy using platelet-cloaked nanoparticles enhances antitumor immunity in solid tumors. Nat. Commun. 2021, 12, 1999.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Wang, Y. X.; Li, Z. T.; Mo, F. Y.; Gu, Z.; Hu, Q. Y. Engineered platelets: Advocates for tumor immunotherapy. Nano Today 2021, 40, 101281.

    Article  CAS  Google Scholar 

  17. Zhou, J. R.; Kroll, A. V.; Holay, M.; Fang, R. H.; Zhang, L. F. Biomimetic nanotechnology toward personalized vaccines. Adv. Mater. 2020, 32, 1901255.

    Article  CAS  Google Scholar 

  18. Fan, X. Y.; Wang, K. Y.; Lu, Q.; Lu, Y. T.; Liu, F. X.; Li, L.; Li, S. H.; Ye, H.; Zhao, J.; Cao, L. P. et al. Surface-anchored tumor microenvironment-responsive protein nanogel-platelet system for cytosolic delivery of therapeutic protein in the post-surgical cancer treatment. Acta Biomater. 2022, 154, 412–423.

    Article  CAS  PubMed  Google Scholar 

  19. Yap, M. L.; McFadyen, J. D.; Wang, X. W.; Zia, N. A.; Hohmann, J. D.; Ziegler, M.; Yao, Y.; Pham, A.; Harris, M.; Donnelly, P. S. et al. Targeting activated platelets: A unique and potentially universal approach for cancer imaging. Theranostics 2017, 7, 2565–2574.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Zhao, W.; Li, T.; Long, Y.; Guo, R.; Sheng, Q. L.; Lu, Z. Z.; Li, M.; Li, J. X.; Zang, S. Y.; Zhang, Z. R. et al. Self-promoted albumin-based nanoparticles for combination therapy against metastatic breast cancer via a hyperthermia-induced “platelet bridge”. ACS Appl. Mater. Interfaces 2021, 13, 25701–25714.

    Article  CAS  PubMed  Google Scholar 

  21. Du, L. Y.; Wang, H. M.; Yang, M.; Liu, L. L.; Niu, Z. Q. Free-standing nanostructured architecture as a promising platform for high-performance lithium-sulfur batteries. Small Struct. 2020, 1, 2000047.

    Article  Google Scholar 

  22. Yang, H. B.; Song, Y. N.; Chen, J.; Pang, Z. Q.; Zhang, N.; Cao, J. T.; Wang, Q. Z.; Li, Q. Y.; Zhang, F.; Dai, Y. X. et al. Platelet membrane-coated nanoparticles target sclerotic aortic valves in ApoE-/- mice by multiple binding mechanisms under pathological shear stress. Int. J. Nanomed. 2020, 15, 901–912.

    Article  CAS  Google Scholar 

  23. Hu, Q. Y.; Sun, W. J.; Qian, C. G.; Wang, C.; Bomba, H. N.; Gu, Z. Anticancer platelet-mimicking nanovehicles. Adv. Mater. 2015, 27, 7043–7050.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Jiang, Q.; Wang, K.; Zhang, X. Y.; Ouyang, B. S.; Liu, H. X.; Pang, Z. Q.; Yang, W. L. Platelet membrane-camouflaged magnetic nanoparticles for ferroptosis-enhanced cancer immunotherapy. Small 2020, 16, 2001704.

    Article  CAS  Google Scholar 

  25. Xu, Z. R.; Zhang, Y. L.; Zhou, W. X.; Wang, L. J.; Xu, G. X.; Ma, M. Z.; Liu, F. H.; Wang, Z.; Wang, Y. C.; Kong, T. T. et al. NIR-II-activated biocompatible hollow nanocarbons for cancer photothermal therapy. J. Nanobiotechnol. 2021, 19, 137.

    Article  CAS  Google Scholar 

  26. Zhang, C.; **a, D. L.; Liu, J. H.; Huo, D.; Jiang, X. Q.; Hu, Y. Bypassing the immunosuppression of myeloid-derived suppressor cells by reversing tumor hypoxia using a platelet-inspired platform. Adv. Funct. Mater. 2020, 30, 2000189.

    Article  CAS  Google Scholar 

  27. Ying, M.; Zhuang, J.; Wei, X. L.; Zhang, X. X.; Zhang, Y.; Jiang, Y.; Dehaini, D.; Chen, M. C.; Gu, S. L.; Gao, W. W. et al. Remote-loaded platelet vesicles for disease-targeted delivery of therapeutics. Adv. Funct. Mater. 2018, 28, 1801032.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Bang, K. H.; Na, Y. G.; Huh, H. W.; Hwang, S. J.; Kim, M. S.; Kim, M.; Lee, H. K.; Cho, C. W. The delivery strategy of paclitaxel nanostructured lipid carrier coated with platelet membrane. Cancers 2019, 11, 807.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Wang, H. J.; Wu, C. H.; Tong, X. W.; Chen, S. J. A biomimetic metal-organic framework nanosystem modulates immunosuppressive tumor microenvironment metabolism to amplify immunotherapy. J. Control. Release 2023, 353, 727–737.

    Article  CAS  PubMed  Google Scholar 

  30. Shang, Y. H.; Wang, Q. H.; Wu, B.; Zhao, Q. Q.; Li, J.; Huang, X. Y.; Chen, W. S.; Gui, R. Platelet-membrane-camouflaged black phosphorus quantum dots enhance anticancer effect mediated by apoptosis and autophagy. ACS Appl. Mater. Interfaces 2019, 11, 28254–28266.

    Article  CAS  PubMed  Google Scholar 

  31. Cho, M. H.; Li, Y.; Lo, P. C.; Lee, H.; Choi, Y. Fucoidan-based theranostic nanogel for enhancing imaging and photodynamic therapy of cancer. Nano-Micro Lett. 2020, 12, 47.

    Article  CAS  Google Scholar 

  32. None. Better nanoparticle targeting with P-selectin. Cancer Discov. 2016, 6, 936.

    Article  Google Scholar 

  33. Stone, J. P.; Wagner, D. D. P-selectin mediates adhesion of platelets to neuroblastoma and small cell lung cancer. J. Clin. Invest. 1993, 92, 804–813.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Hu, Q. Y.; Qian, C. G.; Sun, W. J.; Wang, J. Q.; Chen, Z. W.; Bomba, H. N.; **n, H. L.; Shen, Q. D.; Gu, Z. Engineered nanoplatelets for enhanced treatment of multiple myeloma and thrombus. Adv. Mater. 2016, 28, 9573–9580.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Gibbins, J.; Rana, R.; Khan, D.; Shapiro, S.; Grech, H.; Ramasamy, K. Multiple myeloma treatment is associated with enhanced platelet reactivity. Blood 2018, 132, 3300.

    Article  Google Scholar 

  36. Dehaini, D.; Wei, X. L.; Fang, R. H.; Masson, S.; Angsantikul, P.; Luk, B. T.; Zhang, Y.; Ying, M.; Jiang, Y.; Kroll, A. V. et al. Erythrocyte-platelet hybrid membrane coating for enhanced nanoparticle functionalization. Adv. Mater. 2017, 29, 1606209.

    Article  Google Scholar 

  37. Kim, M. W.; Lee, G.; Niidome, T.; Komohara, Y.; Lee, R.; Park, Y. I. Platelet-like gold nanostars for cancer therapy: The ability to treat cancer and evade immune reactions. Front. Bioeng. Biotechnol. 2020, 8, 133.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Xu, L. L.; Gao, F.; Fan, F.; Yang, L. H. Platelet membrane coating coupled with solar irradiation endows a photodynamic nanosystem with both improved antitumor efficacy and undetectable skin damage. Biomaterials 2018, 159, 59–67.

    Article  CAS  PubMed  Google Scholar 

  39. Chai, Z. H.; **g, C.; Liu, Y.; An, Y. L.; Shi, L. Q. Spectroscopic studies on the photostability and photoactivity of metallotetraphenylporphyrin in micelles. Colloid Polym. Sci. 2014, 292, 1329–1337.

    Article  CAS  Google Scholar 

  40. Deda, D. K.; Araki, K. Nanotechnology, light and chemical action: An effective combination to kill cancer cells. J. Braz. Chem. Soc. 2015, 26, 2448–2470

    CAS  Google Scholar 

  41. Guo, W. H.; Wang, T.; Huang, C. Y.; Ning, S. P.; Guo, Q. L.; Zhang, W.; Yang, H. W.; Zhu, D. M.; Huang, Q. Q.; Qian, H. S. et al. Platelet membrane-coated C-TiO2 hollow nanospheres for combined sonodynamic and alkyl-radical cancer therapy. Nano Res. 2023, 16, 782–791

    Article  CAS  Google Scholar 

  42. Ding, K. L.; Zheng, C. X.; Sun, L. L.; Liu, X. X.; Yin, Y. Y.; Wang, L. NIR light-induced tumor phototherapy using ICG delivery system based on platelet-membrane-camouflaged hollow bismuth selenide nanoparticles. Chin. Chem. Lett. 2020, 31, 1168–1172.

    Article  CAS  Google Scholar 

  43. Bu, L. L.; Rao, L.; Yu, G. T.; Chen, L.; Deng, W. W.; Liu, J. F.; Wu, H.; Meng, Q. F.; Guo, S. S.; Zhao, X. Z. et al. Cancer stem cell-platelet hybrid membrane-coated magnetic nanoparticles for enhanced photothermal therapy of head and neck squamous cell carcinoma. Adv. Funct. Mater. 2019, 29, 1807733.

    Article  Google Scholar 

  44. Rao, L.; Bu, L. L.; Meng, Q. F.; Cai, B.; Deng, W. W.; Li, A.; Li, K. Y.; Guo, S. S.; Zhang, W. F.; Liu, W. et al. Antitumor platelet-mimicking magnetic nanoparticles. Adv. Funct. Mater. 2017, 27, 1604774.

    Article  Google Scholar 

  45. Chen, Y.; Zhao, G. M.; Wang, S.; He, Y. W.; Han, S. L.; Du, C. H.; Li, S. C.; Fan, Z. L.; Wang, C.; Wang, J. P. Platelet-membrane-camouflaged bismuth sulfide nanorods for synergistic radiophotothermal therapy against cancer. Biomater. Sci. 2019, 7, 3450–3459.

    Article  CAS  PubMed  Google Scholar 

  46. Wu, H.; Zhu, J. Q.; Xu, X. F.; **ng, H.; Wang, M. D.; Liang, L.; Li, C.; Jia, H. D.; Shen, F.; Huang, D. S. et al. Biointerfacing antagonizing T-cell inhibitory nanoparticles potentiate hepatocellular carcinoma checkpoint blockade therapy. Small 2021, 17, 2105237.

    Article  CAS  Google Scholar 

  47. Zhou, M.; Lai, W. J.; Li, G. B.; Wang, F. L.; Liu, W. Y.; Liao, J. X.; Yang, H. B.; Liu, Y. L.; Zhang, Q.; Tang, Q. et al. Platelet membrane-coated and VAR2CSA malaria protein-functionalized nanoparticles for targeted treatment of primary and metastatic cancer. ACS Appl. Mater. Interfaces 2021, 13, 25635–25648.

    Article  CAS  PubMed  Google Scholar 

  48. Li, J. H.; Ai, Y. W.; Wang, L. H.; Bu, P. C.; Sharkey, C. C.; Wu, Q. H.; Wun, B.; Roy, S.; Shen, X. L.; King, M. R. Targeted drug delivery to circulating tumor cells via platelet membrane-functionalized particles. Biomaterials 2016, 76, 52–65.

    Article  CAS  PubMed  Google Scholar 

  49. Evans, C. E.; Grover, S. P.; Humphries, J.; Saha, P.; Patel, A. P.; Patel, A. S.; Lyons, O. T.; Waltham, M.; Modarai, B.; Smith, A. Antiangiogenic therapy inhibits venous thrombus resolution. Arterioscler. Thromb. Vasc. Biol. 2014, 34, 565–570.

    Article  CAS  PubMed  Google Scholar 

  50. Ward, Y.; Lake, R.; Faraji, F.; Sperger, J.; Martin, P.; Gilliard, C.; Ku, K. P.; Rodems, T.; Niles, D.; Tillman, H. et al. Platelets promote metastasis via binding tumor CD97 leading to bidirectional signaling that coordinates transendothelial migration. Cell Rep. 2018, 23, 808–822.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Gay, L. J.; Felding-Habermann, B. Contribution of platelets to tumour metastasis. Nat. Rev. Cancer 2011, 11, 123–134.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Cruz, M. A.; Chen, J. M.; Whitelock, J. L.; Morales, L. D.; Lopez, J. A. The platelet glycoprotein Ib-von Willebrand factor interaction activates the collagen receptor α2β1 to bind collagen: Activation-dependent conformational change of the α2-I domain. Blood 2005, 105, 1986–1991.

    Article  CAS  PubMed  Google Scholar 

  53. Wang, S. L.; Wang, R. F.; Meng, N. N.; Guo, H. Y.; Wu, S. Y.; Wang, X. Y.; Li, J. Y.; Wang, H.; Jiang, K.; **e, C. et al. Platelet membrane-functionalized nanoparticles with improved targeting ability and lower hemorrhagic risk for thrombolysis therapy. J. Control. Release 2020, 328, 78–86.

    Article  CAS  PubMed  Google Scholar 

  54. Song, W. T.; Tang, Z. H.; Zhang, D. W.; Li, M. Q.; Gu, J. K.; Chen, X. S. A cooperative polymeric platform for tumor-targeted drug delivery. Chem. Sci. 2016, 7, 728–736.

    Article  CAS  PubMed  Google Scholar 

  55. Li, B. Z.; Chu, T. J.; Wei, J. Y.; Zhang, Y. L.; Qi, F. L.; Lu, Z. F.; Gao, C.; Zhang, T. J.; Jiang, E. S.; Xu, J. C. et al. Platelet-membrane-coated nanoparticles enable vascular disrupting agent combining anti-angiogenic drug for improved tumor vessel impairment. Nano Lett. 2021, 21, 2588–2595.

    Article  CAS  PubMed  Google Scholar 

  56. Koupenova, M.; Clancy, L.; Corkrey, H. A.; Freedman, J. E. Circulating platelets as mediators of immunity, inflammation, and thrombosis. Circ. Res. 2018, 122, 337–351.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. 5Zhang, K.; Ma, Z. Y.; Li, S. T.; Zhang, W. Y.; Foda, M. F.; Zhao, Y. L.; Han, H. Y. Platelet-covered nanocarriers for targeted delivery of hirudin to eliminate thrombotic complication in tumor therapy. ACS Nano 2022, 16, 18483–18496.

    Article  CAS  PubMed  Google Scholar 

  58. Zhang, K.; Long, Y. Y.; Ma, Z. Y.; Li, S. T.; Zhao, Y. L.; Han, H. Y. Artificial nanoplatelet regulation of tumor immune microenvironment to inhibit post-surgical tumor recurrence and lung metastasis. Mater. Today 2023, 67, 68–83.

    Article  CAS  Google Scholar 

  59. Ding, Y. F.; Wang, Z. Y.; Kwong, C. H. T.; Zhao, Y. H.; Mok, G. S. P.; Yu, H. Z.; Wang, R. B. Platelet-mimicking supramolecular nanomedicine with precisely integrated prodrugs for cascade amplification of synergistic chemotherapy. J. Control. Release 2023, 360, 82–92.

    Article  CAS  PubMed  Google Scholar 

  60. Ma, Y. Y.; Zhang, Y. Q.; Han, R.; Li, Y.; Zhai, Y. W.; Qian, Z. Y.; Gu, Y. Q.; Li, S. W. A cascade synergetic strategy induced by photothermal effect based on platelet exosome nanoparticles for tumor therapy. Biomaterials 2022, 282, 121384.

    Article  CAS  PubMed  Google Scholar 

  61. Wallis, S.; Wolska, N.; Englert, H.; Posner, M.; Upadhyay, A.; Renné, T.; Eggleston, I.; Bagby, S.; Pula, G. A peptide from the staphylococcal protein Efb binds P-selectin and inhibits the interaction of platelets with leukocytes. J. Thromb. Haemost. 2022, 20, 729–741.

    Article  CAS  PubMed  Google Scholar 

  62. Liu, Z. M.; Wang, J.; Liao, F. B.; Song, Q. B.; Yao, Y. Tumoreducated platelets facilitate thrombus formation through migration. Front. Oncol. 2022, 12, 857865.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Zhang, T.; Liu, H.; Li, L.; Guo, Z. Y.; Song, J.; Yang, X. Y.; Wan, G. Y.; Li, R. S.; Wang, Y. S. Leukocyte/platelet hybrid membrane-camouflaged dendritic large pore mesoporous silica nanoparticles co-loaded with photo/chemotherapeutic agents for triple negative breast cancer combination treatment. Bioact. Mater. 2021, 6, 3865–3878.

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Chaffer, C. L.; Weinberg, R. A. A perspective on cancer cell metastasis. Science 2011, 331, 1559–1564.

    Article  CAS  PubMed  Google Scholar 

  65. Anderson, R. L.; Balasas, T.; Callaghan, J.; Coombes, R. C.; Evans, J.; Hall, J. A.; Kinrade, S.; Jones, D.; Jones, P. S.; Jones, R. et al. A framework for the development of effective anti-metastatic agents. Nat. Rev. Clin. Oncol. 2019, 16, 185–204.

    Article  PubMed  Google Scholar 

  66. Zhang, L. L.; Zhu, Y. F.; Wei, X. B.; Chen, X.; Li, Y.; Zhu, Y.; **a, J. X.; Huang, Y. H.; Huang, Y. Z.; Wang, J. X. et al. Nanoplateletsomes restrain metastatic tumor formation through decoy and active targeting in a preclinical mouse model. Acta Pharm. Sin. B 2022, 12, 3427–3447.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Plantureux, L.; Mège, D.; Crescence, L.; Carminita, E.; Robert, S.; Cointe, S.; Brouilly, N.; Ezzedine, W.; Dignat-George, F.; Dubois, C. et al. The interaction of platelets with colorectal cancer cells inhibits tumor growth but promotes metastasis. Cancer Res. 2020, 80, 291–303.

    Article  CAS  PubMed  Google Scholar 

  68. Mammadova-Bach, E.; Gil-Pulido, J.; Sarukhanyan, E.; Burkard, P.; Shityakov, S.; Schonhart, C.; Stegner, D.; Remer, K.; Nurden, P.; Nurden, A. T. et al. Platelet glycoprotein VI promotes metastasis through interaction with cancer cell-derived galectin-3. Blood 2020, 135, 1146–1160.

    PubMed  Google Scholar 

  69. Haemmerle, M.; Stone, R. L.; Menter, D. G.; Afshar-Kharghan, V.; Sood, A. K. The platelet lifeline to cancer: Challenges and opportunities. Cancer Cell 2018, 33, 965–983.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Ye, H.; Wang, K. Y.; Wang, M. L.; Liu, R. Z.; Song, H.; Li, N.; Lu, Q.; Zhang, W. J.; Du, Y. Q.; Yang, W. Q. et al. Bioinspired nanoplatelets for chemo-photothermal therapy of breast cancer metastasis inhibition. Biomaterials 2019, 206, 1–12.

    Article  CAS  PubMed  Google Scholar 

  71. Ning, S. P.; Lyu, M.; Zhu, D. M.; Lam, J. W. Y.; Huang, Q. Q.; Zhang, T. F.; Tang, B. Z. Type-I AIE photosensitizer loaded biomimetic system boosting cuproptosis to inhibit breast cancer metastasis and rechallenge. ACS Nano 2023, 17, 10206–10217.

    Article  CAS  PubMed  Google Scholar 

  72. Ning, S. P.; Zhang, T. F.; Lyu, M.; Lam, J. W. Y.; Zhu, D. M.; Huang, Q. Q.; Tang, B. Z. A type I AIE photosensitiser-loaded biomimetic nanosystem allowing precise depletion of cancer stem cells and prevention of cancer recurrence after radiotherapy. Biomaterials 2023, 295, 122034.

    Article  CAS  PubMed  Google Scholar 

  73. Chen, H.; Luo, X.; Huang, Q. H.; Liu, Z. M.; Lyu, M.; Chen, D. X.; Mo, J. L.; Zhu, D. M. Platelet membrane fusion liposome loaded with type I AIE photosensitizer to induce chemoresistance cancer pyroptosis and immunogenic cell death for enhancing cancer immunotherapy. Chem. Eng. J. 2023, 476, 146276.

    Article  CAS  Google Scholar 

  74. Zhao, H. J.; Zhao, B. B.; Li, L.; Ding, K. L.; **ao, H. F.; Zheng, C. X.; Sun, L. L.; Zhang, Z. Z.; Wang, L. Biomimetic decoy inhibits tumor growth and lung metastasis by reversing the drawbacks of sonodynamic therapy. Adv. Healthc. Mater. 2020, 9, 1901335

    Article  CAS  Google Scholar 

  75. Rao, L.; Meng, Q. F.; Huang, Q. Q.; Wang, Z. X.; Yu, G. T.; Li, A.; Ma, W. J.; Zhang, N. G.; Guo, S. S.; Zhao, X. Z. et al. Platelet-leukocyte hybrid membrane-coated immunomagnetic beads for highly efficient and highly specific isolation of circulating tumor cells. Adv. Funct. Mater. 2018, 28, 1803531.

    Article  Google Scholar 

  76. Luo, Z. M.; Lu, L. W.; Xu, W. X.; Meng, N. N.; Wu, S. Y.; Zhou, J. F.; Xu, Q. Z.; **e, C.; Liu, Y.; Lu, W. Y. In vivo self-assembled drug nanocrystals for metastatic breast cancer all-stage targeted therapy. J. Control. Release 2022, 346, 32–42.

    Article  CAS  PubMed  Google Scholar 

  77. Scherlinger, M.; Richez, C.; Tsokos, G. C.; Boilard, E.; Blanco, P. The role of platelets in immune-mediated inflammatory diseases. Nat. Rev. Immunol. 2023, 23, 495–510.

    Article  CAS  PubMed  Google Scholar 

  78. Li, T.; Chen, T. T.; Chen, H.; Wang, Q.; Liu, Z. Y.; Fang, L. Y.; Wan, M. M.; Mao, C.; Shen, J. Engineered platelet-based micro/nanomotors for cancer therapy. Small 2021, 17, 2104912.

    Article  CAS  Google Scholar 

  79. Hu, Q. Y.; Li, H. J.; Archibong, E.; Chen, Q.; Ruan, H. T.; Ahn, S.; Dukhovlinova, E.; Kang, Y.; Wen, D.; Dotti, G. et al. Inhibition of post-surgery tumour recurrence via a hydrogel releasing CAR-T cells and anti-PDL1-conjugated platelets. Nat. Biomed. Eng. 2021, 5, 1038–1047.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Li, Z. T.; Ding, Y. Y.; Liu, J.; Wang, J. X.; Mo, F. Y.; Wang, Y. X.; Chen-Mayfield, T. J.; Sondel, P. M.; Hong, S.; Hu, Q. Y. Depletion of tumor associated macrophages enhances local and systemic platelet-mediated anti-PD-1 delivery for post-surgery tumor recurrence treatment. Nat. Commun. 2022, 13, 1845.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Zhang, X. D.; Wang, J. Q.; Chen, Z. W.; Hu, Q. Y.; Wang, C.; Yan, J. J.; Dotti, G.; Huang, P.; Gu, Z. Engineering PD-1-presenting platelets for cancer immunotherapy. Nano Lett. 2018, 18, 5716–5725.

    Article  CAS  PubMed  Google Scholar 

  82. Lu, Q.; Ye, H.; Wang, K. Y.; Zhao, J.; Wang, H. L.; Song, J. X.; Fan, X. Y.; Lu, Y. T.; Cao, L. P.; Wan, B. et al. Bioengineered platelets combining chemotherapy and immunotherapy for postsurgical melanoma treatment: Internal core-loaded doxorubicin and external surface-anchored anti-PD-L1 antibody backpacks. Nano Lett. 2022, 22, 3141–3150.

    Article  CAS  PubMed  Google Scholar 

  83. Tang, S. S.; Zhang, F. Y.; Gong, H.; Wei, F. N.; Zhuang, J.; Karshalev, E.; Esteban-Fernández de Ávila, B.; Huang, C. Y.; Zhou, Z. D.; Li, Z. X. et al. Enzyme-powered Janus platelet cell robots for active and targeted drug delivery. Sci. Robot. 2020, 5, eaba6137.

    Article  PubMed  Google Scholar 

  84. Yang, Y. X.; Wang, Y. F.; Yao, Y. J.; Wang, S. Q.; Zhang, Y. Q.; Dotti, G.; Yu, J. C.; Gu, Z. T cell-mimicking platelet-drug conjugates. Matter 2023, 6, 2340–2355.

    Article  CAS  Google Scholar 

  85. Wang, C.; Sun, W. J.; Ye, Y. Q.; Hu, Q. Y.; Bomba, H. N.; Gu, Z. In situ activation of platelets with checkpoint inhibitors for post-surgical cancer immunotherapy. Nat. Biomed. Eng. 2017, 1, 0011.

    Article  CAS  Google Scholar 

  86. Hu, Q. Y.; Sun, W. J.; Wang, J. Q.; Ruan, H. T.; Zhang, X. D.; Ye, Y. Q.; Shen, S.; Wang, C.; Lu, W. Y.; Cheng, K. et al. Conjugation of haematopoietic stem cells and platelets decorated with anti-PD-1 antibodies augments anti-leukaemia efficacy. Nat. Biomed. Eng. 2018, 2, 831–840.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Lv, Y. L.; Li, F.; Wang, S.; Lu, G. H.; Bao, W. E.; Wang, Y. G.; Tian, Z. Y.; Wei, W.; Ma, G. H. Near-infrared light-triggered platelet arsenal for combined photothermal-immunotherapy against cancer. Sci. Adv. 2021, 7, eabd7614.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Li, H. J.; Wang, Z. J.; Chen, Z. W.; Ci, T.; Chen, G. J.; Wen, D.; Li, R. X.; Wang, J. Q.; Meng, H.; Bryan Bell, R. et al. Disrupting tumour vasculature and recruitment of aPDL1-loaded platelets control tumour metastasis. Nat. Commun. 2021, 12, 2773.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Xu, P. P.; Zuo, H. Q.; Chen, B.; Wang, R. J.; Ahmed, A.; Hu, Y.; Ouyang, J. Doxorubicin-loaded platelets as a smart drug delivery system: An improved therapy for lymphoma. Sci. Rep. 2017, 7, 42632.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Braun, A.; Anders, H. J.; Gudermann, T.; Mammadova-Bach, E. Platelet-cancer interplay: Molecular mechanisms and new therapeutic avenues. Front. Oncol. 2021, 11, 665534.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Xu, X. R.; Carrim, N.; Neves, M. A. D.; McKeown, T.; Stratton, T. W.; Coelho, R. M. P.; Lei, X.; Chen, P. G.; Xu, J. H.; Dai, X. R. et al. Platelets and platelet adhesion molecules: Novel mechanisms of thrombosis and anti-thrombotic therapies. Thromb. J. 2016, 14, 29.

    Article  PubMed  PubMed Central  Google Scholar 

  92. Lippi, G.; Franchini, M.; Targher, G. Arterial thrombus formation in cardiovascular disease. Nat. Rev. Cardiol. 2011, 8, 502–512.

    Article  PubMed  Google Scholar 

  93. Han, X.; Chen, J. W.; Chu, J. C.; Liang, C.; Ma, Q. L.; Fan, Q.; Liu, Z.; Wang, C. Platelets as platforms for inhibition of tumor recurrence post-physical therapy by delivery of anti-PD-L1 checkpoint antibody. J. Control. Release 2019, 304, 233–241.

    Article  CAS  PubMed  Google Scholar 

  94. Rao, L.; Bu, L. L.; Ma, L.; Wang, W. B.; Liu, H. Q.; Wan, D.; Liu, J. F.; Li, A.; Guo, S. S.; Zhang, L. et al. Platelet-facilitated photothermal therapy of head and neck squamous cell carcinoma. Angew. Chem., Int. Ed. 2018, 57, 986–991.

    Article  CAS  Google Scholar 

  95. Wang, Y. X.; Li, W.; Li, Z. T.; Mo, F. Y.; Chen, Y.; Iida, M.; Wheeler, D. L.; Hu, Q. Y. Active recruitment of anti-PD-1-conjugated platelets through tumor-selective thrombosis for enhanced anticancer immunotherapy. Sci. Adv. 2023, 9, eadf6854.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Fan, J. X.; Liu, X. H.; Wang, X. N.; Niu, M. T.; Chen, Q. W.; Zheng, D. W.; Wei, J. S.; Yang, X. Q.; Zeng, X.; Zhang, X. Z. Antibody engineered platelets attracted by bacteria-induced tumorspecific blood coagulation for checkpoint inhibitor immunotherapy. Adv. Funct. Mater. 2021, 31, 2009744.

    Article  CAS  Google Scholar 

  97. Nishikawa, T.; Tung, L. Y.; Kaneda, Y. Systemic administration of platelets incorporating inactivated Sendai virus eradicates melanoma in mice. Mol. Ther. 2014, 22, 2046–2055.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Sim, X.; Poncz, M.; Gadue, P.; French, D. L. Understanding platelet generation from megakaryocytes: Implications for in vitro-derived platelets. Blood 2016, 127, 1227–1233.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Figueiredo, C.; Blasczyk, R. Generation of HLA universal megakaryocytes and platelets by genetic engineering. Front. Immunol. 2021, 12, 768458.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Yap, M. L.; McFadyen, J. D.; Wang, X. W.; Ziegler, M.; Chen, Y. C.; Willcox, A.; Nowell, C. J.; Scott, A. M.; Sloan, E. K.; Hogarth, P. M. et al. Activated platelets in the tumor microenvironment for targeting of antibody-drug conjugates to tumors and metastases. Theranostics 2019, 9, 1154–1169.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Cao, J. X.; Yang, P.; Wang, P. Z.; Xu, S. T.; Cheng, Y. L.; Qian, K.; Xu, M. J.; Sheng, D. Y.; Li, Y. X.; Wei, Y. et al. ‘Adhesion and release’ nanoparticle-mediated efficient inhibition of platelet activation disrupts endothelial barriers for enhanced drug delivery in tumors. Biomaterials 2021, 269, 120620.

    Article  CAS  PubMed  Google Scholar 

  102. Li, S. J.; Li, L.; Lin, X.; Chen, C.; Luo, C. H.; Huang, Y. Targeted inhibition of tumor inflammation and tumor-platelet crosstalk by nanoparticle-mediated drug delivery mitigates cancer metastasis. ACS Nano 2022, 16, 50–67.

    Article  CAS  PubMed  Google Scholar 

  103. Zhang, Y. J.; Zhu, X.; Chen, X. L.; Chen, Q. J.; Zhou, W. X.; Guo, Q.; Lu, Y. F.; Li, C.; Zhang, Y.; Liang, D. H. et al. Activated platelets-targeting micelles with controlled drug release for effective treatment of primary and metastatic triple negative breast cancer. Adv. Funct. Mater. 2019, 29, 1806620.

    Article  Google Scholar 

  104. Guo, R.; Deng, M.; He, X.; Li, M. M.; Li, J. X.; He, P. H.; Liu, H. Q.; Li, M.; Zhang, Z. R.; He, Q. Fucoidan-functionalized activated platelet-hitchhiking micelles simultaneously track tumor cells and remodel the immunosuppressive microenvironment for efficient metastatic cancer treatment. Acta Pharm. Sin. B 2022, 12, 467–482.

    Article  CAS  PubMed  Google Scholar 

  105. Song, Y. N.; Zhang, N.; Li, Q. Y.; Chen, J.; Wang, Q. Z.; Yang, H. B.; Tan, H. P.; Gao, J. F.; Dong, Z. H.; Pang, Z. Q. et al. Biomimetic liposomes hybrid with platelet membranes for targeted therapy of atherosclerosis. Chem. Eng. J. 2021, 408, 127296.

    Article  CAS  Google Scholar 

  106. Hu, S. Q.; Wang, X. Y.; Li, Z. H.; Zhu, D. S.; Cores, J.; Wang, Z. Z.; Li, J. L.; Mei, X.; Cheng, X.; Su, T. et al. Platelet membrane and stem cell exosome hybrids enhance cellular uptake and targeting to heart injury. Nano Today 2021, 39, 101210.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. **, P. P.; Wang, L. S.; Sha, R.; Liu, L.; Qian, J. Y.; Ishimwe, N.; Zhang, W. B.; Qian, J.; Zhang, Y. J.; Wen, L. P. A blood circulation-prolonging peptide anchored biomimetic phage-platelet hybrid nanoparticle system for prolonged blood circulation and optimized anti-bacterial performance. Theranostics 2021, 11, 2278–2296.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Zhang, Y.; Ma, K. L.; Gong, Y. X.; Wang, G. H.; Hu, Z. B.; Liu, L.; Lu, J.; Chen, P. P.; Lu, C. C.; Ruan, X. Z. et al. Platelet microparticles mediate glomerular endothelial injury in early diabetic nephropathy. J. Am. Soc. Nephrol. 2018, 29, 2671–2695.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Zhang, X. D.; Kang, Y.; Wang, J. Q.; Yan, J. J.; Chen, Q.; Cheng, H.; Huang, P.; Gu, Z. Engineered PD-L1-expressing platelets reverse new-onset type 1 diabetes. Adv. Mater. 2020, 32, 1907692.

    Article  CAS  Google Scholar 

  110. Mezouar, S.; Frère, C.; Darbousset, R.; Mege, D.; Crescence, L.; Dignat-George, F.; Panicot-Dubois, L.; Dubois, C. Role of platelets in cancer and cancer-associated thrombosis: Experimental and clinical evidences. Thromb. Res. 2016, 139, 65–76.

    Article  CAS  PubMed  Google Scholar 

  111. Servais, L.; Wéra, O.; Epoh, J. D.; Delierneux, C.; Bouznad, N.; Rahmouni, S.; Mazzucchelli, G.; Baiwir, D.; Delvenne, P.; Lancellotti, P. et al. Platelets contribute to the initiation of colitis-associated cancer by promoting immunosuppression. J. Thromb. Haemost. 2018, 16, 762–777.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Key Research and Development Program of China (Nos. 2022YFC2402400 and 2023YFA0915400), Guangdong Provincial Key Area R&D Program (No. 2020B1111540001), the Natural Science Foundation of Guangdong Province (Nos. 2024A1515010825, 2024A1515030063, 2022A1515010780, and 2022A1515011337), Guangdong Province Universities and Colleges Characteristic Innovation (No. 2021KTSCX036), Traditional Chinese Medicine Research Project of Guangdong Province Traditional Chinese Medicine Bureau (No. 20221206), Shenzhen Medical Research Fund (No. A2303057), Discipline Construction Project of Guangdong Medical University (No. 4SG24015G), Construction Project of Nano Technology and Application Engineering Research Center of Guangdong Medical University (No. 4SG24179G) and Funds for PHD researchers of Guangdong Medical University in 2024.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Lintao Cai, Ting Yin or Hong Pan.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cai, X., Qiu, L., Diao, Z. et al. Platelet-based bioactive systems guided precision targeting and immune regulation for cancer therapy. Nano Res. (2024). https://doi.org/10.1007/s12274-024-6777-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12274-024-6777-0

Keywords

Navigation