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Active recruitment of anti–PD-1–conjugated platelets through tumor-selective thrombosis for enhanced anticancer immunotherapy

Immune checkpoint inhibitors (ICIs) can reinvigorate T cells to eradicate tumor cells, showing great potential in combating various types of tumors. We propose a delivery strategy to enhance tumor-selective ICI accumulation, which leverages the responsiveness of platelets and platelet-derivatives to...

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Autores principales: Wang, Yixin, Li, Wen, Li, Zhaoting, Mo, Fanyi, Chen, Yu, Iida, Mari, Wheeler, Deric L, Hu, Quanyin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10058243/
https://www.ncbi.nlm.nih.gov/pubmed/36989364
http://dx.doi.org/10.1126/sciadv.adf6854
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author Wang, Yixin
Li, Wen
Li, Zhaoting
Mo, Fanyi
Chen, Yu
Iida, Mari
Wheeler, Deric L
Hu, Quanyin
author_facet Wang, Yixin
Li, Wen
Li, Zhaoting
Mo, Fanyi
Chen, Yu
Iida, Mari
Wheeler, Deric L
Hu, Quanyin
author_sort Wang, Yixin
collection PubMed
description Immune checkpoint inhibitors (ICIs) can reinvigorate T cells to eradicate tumor cells, showing great potential in combating various types of tumors. We propose a delivery strategy to enhance tumor-selective ICI accumulation, which leverages the responsiveness of platelets and platelet-derivatives to coagulation cascade signals. A fused protein tTF-RGD targets tumor angiogenic blood vessel endothelial cells and initiates the coagulation locoregionally at the tumor site, forming a “cellular hive” to recruit anti–PD-1 antibody (aPD-1)–conjugated platelets to the tumor site and subsequently activating platelets to release aPD-1 antibody to reactivate T cells for improved immunotherapy. Moreover, on a patient-derived xenograft breast cancer model, the platelet membrane–coated nanoparticles can also respond to the coagulation signals initiated by tTF-RGD, thus enhancing the accumulation and antitumor efficacy of the loaded chemotherapeutics. Our study illustrates a versatile platform technology to enhance the local accumulation of ICIs and chemodrugs by taking advantage of the responsiveness of platelets and platelet derivatives to thrombosis.
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spelling pubmed-100582432023-03-30 Active recruitment of anti–PD-1–conjugated platelets through tumor-selective thrombosis for enhanced anticancer immunotherapy Wang, Yixin Li, Wen Li, Zhaoting Mo, Fanyi Chen, Yu Iida, Mari Wheeler, Deric L Hu, Quanyin Sci Adv Biomedicine and Life Sciences Immune checkpoint inhibitors (ICIs) can reinvigorate T cells to eradicate tumor cells, showing great potential in combating various types of tumors. We propose a delivery strategy to enhance tumor-selective ICI accumulation, which leverages the responsiveness of platelets and platelet-derivatives to coagulation cascade signals. A fused protein tTF-RGD targets tumor angiogenic blood vessel endothelial cells and initiates the coagulation locoregionally at the tumor site, forming a “cellular hive” to recruit anti–PD-1 antibody (aPD-1)–conjugated platelets to the tumor site and subsequently activating platelets to release aPD-1 antibody to reactivate T cells for improved immunotherapy. Moreover, on a patient-derived xenograft breast cancer model, the platelet membrane–coated nanoparticles can also respond to the coagulation signals initiated by tTF-RGD, thus enhancing the accumulation and antitumor efficacy of the loaded chemotherapeutics. Our study illustrates a versatile platform technology to enhance the local accumulation of ICIs and chemodrugs by taking advantage of the responsiveness of platelets and platelet derivatives to thrombosis. American Association for the Advancement of Science 2023-03-29 /pmc/articles/PMC10058243/ /pubmed/36989364 http://dx.doi.org/10.1126/sciadv.adf6854 Text en Copyright © 2023 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (https://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.
spellingShingle Biomedicine and Life Sciences
Wang, Yixin
Li, Wen
Li, Zhaoting
Mo, Fanyi
Chen, Yu
Iida, Mari
Wheeler, Deric L
Hu, Quanyin
Active recruitment of anti–PD-1–conjugated platelets through tumor-selective thrombosis for enhanced anticancer immunotherapy
title Active recruitment of anti–PD-1–conjugated platelets through tumor-selective thrombosis for enhanced anticancer immunotherapy
title_full Active recruitment of anti–PD-1–conjugated platelets through tumor-selective thrombosis for enhanced anticancer immunotherapy
title_fullStr Active recruitment of anti–PD-1–conjugated platelets through tumor-selective thrombosis for enhanced anticancer immunotherapy
title_full_unstemmed Active recruitment of anti–PD-1–conjugated platelets through tumor-selective thrombosis for enhanced anticancer immunotherapy
title_short Active recruitment of anti–PD-1–conjugated platelets through tumor-selective thrombosis for enhanced anticancer immunotherapy
title_sort active recruitment of anti–pd-1–conjugated platelets through tumor-selective thrombosis for enhanced anticancer immunotherapy
topic Biomedicine and Life Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10058243/
https://www.ncbi.nlm.nih.gov/pubmed/36989364
http://dx.doi.org/10.1126/sciadv.adf6854
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