Surface‐Anchored Ticagrelor Gelatin Nanoparticles‐Platelets System for Enhanced Anti‐PD‐L1 Therapy Response and Boosted Chemotherapeutic Efficacy of Nanomedicines
ABSTRACT The tumor microenvironment is characterized by immunosuppression and compromised intratumoral perfusion, which impairs the effectiveness of immune checkpoint inhibitors and nanomedicines. A significant challenge is the role of activated platelets, as they increase transfer‐mediated PD‐L1 ex...
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Wiley
2025-06-01
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| Series: | Exploration |
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| Online Access: | https://doi.org/10.1002/EXP.20240084 |
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| author | Qi Lu Hao Ye Jian Zhao Xiaoyuan Fan Kaiyuan Wang Zeyu Han Tian Liu Lili Du Jiaxuan Song Helin Wang Haotian Zhang Zhonggui He Jin Sun |
| author_facet | Qi Lu Hao Ye Jian Zhao Xiaoyuan Fan Kaiyuan Wang Zeyu Han Tian Liu Lili Du Jiaxuan Song Helin Wang Haotian Zhang Zhonggui He Jin Sun |
| author_sort | Qi Lu |
| collection | DOAJ |
| description | ABSTRACT The tumor microenvironment is characterized by immunosuppression and compromised intratumoral perfusion, which impairs the effectiveness of immune checkpoint inhibitors and nanomedicines. A significant challenge is the role of activated platelets, as they increase transfer‐mediated PD‐L1 expression from tumor cells and maintain the integrity of tumor vasculature. These platelets support tumor growth by stabilizing the vasculature and enabling immune evasion, as well as shielding tumor cells from immune detection. To address these platelet‐mediated negative antitumor effects, we have developed bioengineered platelets (PTNPs) with surface‐anchored ticagrelor‐loaded gelatin nanoparticles. This study utilizes the natural tendency of platelets to localize their activated counterparts into tumors. Upon binding to tumor‐associated activated platelets, the PTNPs release ticagrelor in response to the secreted matrix metalloproteinases by activated platelet, inhibiting further platelet activation. This reduction in platelet activation lessens platelet‐facilitated immunosuppression and diminishes the transferred‐PD‐L1 expression from cancer cells to platelets, thus enhancing the immune response of anti‐PD‐L1 therapy. Additionally, this strategy weakens the activated platelets’ contribution to tumor vascular integrity, improving the extravasation and chemotherapeutic efficacy of nanomedicines. Our findings highlight the crucial role of platelet activation in tumor biology and introduce PTNPs as an effective approach to disrupt tumor‐supporting platelet activities and enhance anticancer treatments efficacy. |
| format | Article |
| id | doaj-art-554a97fb7c7741c2bbfeaf8d4648746c |
| institution | OA Journals |
| issn | 2766-8509 2766-2098 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | Exploration |
| spelling | doaj-art-554a97fb7c7741c2bbfeaf8d4648746c2025-08-20T02:36:23ZengWileyExploration2766-85092766-20982025-06-0153n/an/a10.1002/EXP.20240084Surface‐Anchored Ticagrelor Gelatin Nanoparticles‐Platelets System for Enhanced Anti‐PD‐L1 Therapy Response and Boosted Chemotherapeutic Efficacy of NanomedicinesQi Lu0Hao Ye1Jian Zhao2Xiaoyuan Fan3Kaiyuan Wang4Zeyu Han5Tian Liu6Lili Du7Jiaxuan Song8Helin Wang9Haotian Zhang10Zhonggui He11Jin Sun12Department of Pharmaceutics Wuya College of Innovation Shenyang Pharmaceutical University Shenyang Liaoning P. R. ChinaMulti‐Scale Robotics Lab (MSRL) Institute of Robotics & Intelligent Systems (IRIS) ETH Zurich Zurich SwitzerlandDepartment of Pharmaceutics Wuya College of Innovation Shenyang Pharmaceutical University Shenyang Liaoning P. R. ChinaDepartment of Pharmaceutics Wuya College of Innovation Shenyang Pharmaceutical University Shenyang Liaoning P. R. ChinaDepartment of Pharmaceutics Wuya College of Innovation Shenyang Pharmaceutical University Shenyang Liaoning P. R. ChinaDepartment of Pharmaceutics Wuya College of Innovation Shenyang Pharmaceutical University Shenyang Liaoning P. R. ChinaDepartment of Pharmaceutics Wuya College of Innovation Shenyang Pharmaceutical University Shenyang Liaoning P. R. ChinaDepartment of Pharmaceutics Wuya College of Innovation Shenyang Pharmaceutical University Shenyang Liaoning P. R. ChinaDepartment of Pharmaceutics Wuya College of Innovation Shenyang Pharmaceutical University Shenyang Liaoning P. R. ChinaDepartment of Pharmaceutics Wuya College of Innovation Shenyang Pharmaceutical University Shenyang Liaoning P. R. ChinaSchool of Life Science and Biopharmaceutics Shenyang Pharmaceutical University Shenyang Liaoning P. R. ChinaDepartment of Pharmaceutics Wuya College of Innovation Shenyang Pharmaceutical University Shenyang Liaoning P. R. ChinaDepartment of Pharmaceutics Wuya College of Innovation Shenyang Pharmaceutical University Shenyang Liaoning P. R. ChinaABSTRACT The tumor microenvironment is characterized by immunosuppression and compromised intratumoral perfusion, which impairs the effectiveness of immune checkpoint inhibitors and nanomedicines. A significant challenge is the role of activated platelets, as they increase transfer‐mediated PD‐L1 expression from tumor cells and maintain the integrity of tumor vasculature. These platelets support tumor growth by stabilizing the vasculature and enabling immune evasion, as well as shielding tumor cells from immune detection. To address these platelet‐mediated negative antitumor effects, we have developed bioengineered platelets (PTNPs) with surface‐anchored ticagrelor‐loaded gelatin nanoparticles. This study utilizes the natural tendency of platelets to localize their activated counterparts into tumors. Upon binding to tumor‐associated activated platelets, the PTNPs release ticagrelor in response to the secreted matrix metalloproteinases by activated platelet, inhibiting further platelet activation. This reduction in platelet activation lessens platelet‐facilitated immunosuppression and diminishes the transferred‐PD‐L1 expression from cancer cells to platelets, thus enhancing the immune response of anti‐PD‐L1 therapy. Additionally, this strategy weakens the activated platelets’ contribution to tumor vascular integrity, improving the extravasation and chemotherapeutic efficacy of nanomedicines. Our findings highlight the crucial role of platelet activation in tumor biology and introduce PTNPs as an effective approach to disrupt tumor‐supporting platelet activities and enhance anticancer treatments efficacy.https://doi.org/10.1002/EXP.20240084chemotherapyimmunotherapyMMPs‐responsive releaseplatelet‐based delivery systemtumor‐associated platelets |
| spellingShingle | Qi Lu Hao Ye Jian Zhao Xiaoyuan Fan Kaiyuan Wang Zeyu Han Tian Liu Lili Du Jiaxuan Song Helin Wang Haotian Zhang Zhonggui He Jin Sun Surface‐Anchored Ticagrelor Gelatin Nanoparticles‐Platelets System for Enhanced Anti‐PD‐L1 Therapy Response and Boosted Chemotherapeutic Efficacy of Nanomedicines Exploration chemotherapy immunotherapy MMPs‐responsive release platelet‐based delivery system tumor‐associated platelets |
| title | Surface‐Anchored Ticagrelor Gelatin Nanoparticles‐Platelets System for Enhanced Anti‐PD‐L1 Therapy Response and Boosted Chemotherapeutic Efficacy of Nanomedicines |
| title_full | Surface‐Anchored Ticagrelor Gelatin Nanoparticles‐Platelets System for Enhanced Anti‐PD‐L1 Therapy Response and Boosted Chemotherapeutic Efficacy of Nanomedicines |
| title_fullStr | Surface‐Anchored Ticagrelor Gelatin Nanoparticles‐Platelets System for Enhanced Anti‐PD‐L1 Therapy Response and Boosted Chemotherapeutic Efficacy of Nanomedicines |
| title_full_unstemmed | Surface‐Anchored Ticagrelor Gelatin Nanoparticles‐Platelets System for Enhanced Anti‐PD‐L1 Therapy Response and Boosted Chemotherapeutic Efficacy of Nanomedicines |
| title_short | Surface‐Anchored Ticagrelor Gelatin Nanoparticles‐Platelets System for Enhanced Anti‐PD‐L1 Therapy Response and Boosted Chemotherapeutic Efficacy of Nanomedicines |
| title_sort | surface anchored ticagrelor gelatin nanoparticles platelets system for enhanced anti pd l1 therapy response and boosted chemotherapeutic efficacy of nanomedicines |
| topic | chemotherapy immunotherapy MMPs‐responsive release platelet‐based delivery system tumor‐associated platelets |
| url | https://doi.org/10.1002/EXP.20240084 |
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