Bone marrow-targeted thrombopoietin delivery via engineered platelet-derived vesicle-loaded dissolving microneedles for treating ionizing radiation-induced injury
Exposure to a nuclear accident or a radiological attack may cause serious death events due to hematopoietic acute radiation syndrome (H-ARS). While thrombopoietin (TPO) shows promise in mitigating myelosuppression, its clinical use is restricted due to high doses, strict schedules, and systemic toxi...
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Elsevier
2025-08-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590006425005502 |
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| author | Zhenchao Ma Yuntao Li Jiawei Zhu Sheng Qiu Yingrong Chen Hengbin Cao Shuixin Yang Xueli Jia Lixia Huo Qian Shi Shunwen Han Hao Chang Xiang Yu |
| author_facet | Zhenchao Ma Yuntao Li Jiawei Zhu Sheng Qiu Yingrong Chen Hengbin Cao Shuixin Yang Xueli Jia Lixia Huo Qian Shi Shunwen Han Hao Chang Xiang Yu |
| author_sort | Zhenchao Ma |
| collection | DOAJ |
| description | Exposure to a nuclear accident or a radiological attack may cause serious death events due to hematopoietic acute radiation syndrome (H-ARS). While thrombopoietin (TPO) shows promise in mitigating myelosuppression, its clinical use is restricted due to high doses, strict schedules, and systemic toxicity from conventional administration. This study developed a dissolving microneedle patch loaded with engineered activated platelet-derived vesicles encapsulating TPO (TLEVs@MN) for targeted treatment of H-ARS. Activated platelet-derived vesicles were isolated via ultracentrifugation and then modified with glutathione. Glutathione-based anti-ROS modification effectively protected vesicles from radiation-induced oxidative damage, enhancing their stability and targeting efficiency. Using mild sonication, TPO was efficiently encapsulated into engineered vesicles without compromising membrane protein integrity. Further loading into dissolving MNs facilitated minimally invasive transdermal delivery while ensuring long-term vesicle stability during storage. TLEVs@MNs effectively activated the JAK2/STAT3 pathway, restoring mitochondrial function in hematopoietic stem cells. Pharmacokinetic and biodistribution analyses demonstrated that administration of TPO using TLEVs@MNs achieved the precise TPO delivery to bone marrow hematopoietic stem and progenitor cells, significantly improving survival rates and hematopoietic recovery in irradiated animal models. These findings highlighted TLEVs@MN patch as a promosing and robust TPO delivery platform for managing IR-induced hematopoietic injury. |
| format | Article |
| id | doaj-art-01028343e1fc4e0dab92df6835730239 |
| institution | OA Journals |
| issn | 2590-0064 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Materials Today Bio |
| spelling | doaj-art-01028343e1fc4e0dab92df68357302392025-08-20T02:06:57ZengElsevierMaterials Today Bio2590-00642025-08-013310198010.1016/j.mtbio.2025.101980Bone marrow-targeted thrombopoietin delivery via engineered platelet-derived vesicle-loaded dissolving microneedles for treating ionizing radiation-induced injuryZhenchao Ma0Yuntao Li1Jiawei Zhu2Sheng Qiu3Yingrong Chen4Hengbin Cao5Shuixin Yang6Xueli Jia7Lixia Huo8Qian Shi9Shunwen Han10Hao Chang11Xiang Yu12Affiliated Huzhou Hospital, Zhejiang University School of Medicine, Huzhou Central Hospital, Huzhou, 313000, Zhejiang, China; School of Medicine, Huzhou University, Huzhou 313000, Zhejiang, ChinaAffiliated Huzhou Hospital, Zhejiang University School of Medicine, Huzhou Central Hospital, Huzhou, 313000, Zhejiang, ChinaWenzhou Medical University, School of Pharmacy, Wenzhou, 325035, Zhejiang, ChinaAffiliated Huzhou Hospital, Zhejiang University School of Medicine, Huzhou Central Hospital, Huzhou, 313000, Zhejiang, ChinaAffiliated Huzhou Hospital, Zhejiang University School of Medicine, Huzhou Central Hospital, Huzhou, 313000, Zhejiang, ChinaAffiliated Huzhou Hospital, Zhejiang University School of Medicine, Huzhou Central Hospital, Huzhou, 313000, Zhejiang, ChinaAffiliated Huzhou Hospital, Zhejiang University School of Medicine, Huzhou Central Hospital, Huzhou, 313000, Zhejiang, ChinaDepartment of Pharmaceutical Science, School of Pharmacy, Naval Medical University, 800 Xiangyin Road, Shanghai, 200433, ChinaSchool of Medicine, Huzhou University, Huzhou 313000, Zhejiang, ChinaSchool of Medicine, Huzhou University, Huzhou 313000, Zhejiang, ChinaAffiliated Huzhou Hospital, Zhejiang University School of Medicine, Huzhou Central Hospital, Huzhou, 313000, Zhejiang, China; Corresponding author.Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou, 310022, Zhejiang, China; Corresponding author.Affiliated Huzhou Hospital, Zhejiang University School of Medicine, Huzhou Central Hospital, Huzhou, 313000, Zhejiang, China; School of Medicine, Huzhou University, Huzhou 313000, Zhejiang, China; Corresponding author. Affiliated Huzhou Hospital, Zhejiang University School of Medicine, Huzhou Central Hospital, Huzhou, 313000, Zhejiang, China.Exposure to a nuclear accident or a radiological attack may cause serious death events due to hematopoietic acute radiation syndrome (H-ARS). While thrombopoietin (TPO) shows promise in mitigating myelosuppression, its clinical use is restricted due to high doses, strict schedules, and systemic toxicity from conventional administration. This study developed a dissolving microneedle patch loaded with engineered activated platelet-derived vesicles encapsulating TPO (TLEVs@MN) for targeted treatment of H-ARS. Activated platelet-derived vesicles were isolated via ultracentrifugation and then modified with glutathione. Glutathione-based anti-ROS modification effectively protected vesicles from radiation-induced oxidative damage, enhancing their stability and targeting efficiency. Using mild sonication, TPO was efficiently encapsulated into engineered vesicles without compromising membrane protein integrity. Further loading into dissolving MNs facilitated minimally invasive transdermal delivery while ensuring long-term vesicle stability during storage. TLEVs@MNs effectively activated the JAK2/STAT3 pathway, restoring mitochondrial function in hematopoietic stem cells. Pharmacokinetic and biodistribution analyses demonstrated that administration of TPO using TLEVs@MNs achieved the precise TPO delivery to bone marrow hematopoietic stem and progenitor cells, significantly improving survival rates and hematopoietic recovery in irradiated animal models. These findings highlighted TLEVs@MN patch as a promosing and robust TPO delivery platform for managing IR-induced hematopoietic injury.http://www.sciencedirect.com/science/article/pii/S2590006425005502MicroneedleActivated platelet-derived vesiclesThrombopoietinIonizing radiationMitochondriaHematopoietic stem cells |
| spellingShingle | Zhenchao Ma Yuntao Li Jiawei Zhu Sheng Qiu Yingrong Chen Hengbin Cao Shuixin Yang Xueli Jia Lixia Huo Qian Shi Shunwen Han Hao Chang Xiang Yu Bone marrow-targeted thrombopoietin delivery via engineered platelet-derived vesicle-loaded dissolving microneedles for treating ionizing radiation-induced injury Materials Today Bio Microneedle Activated platelet-derived vesicles Thrombopoietin Ionizing radiation Mitochondria Hematopoietic stem cells |
| title | Bone marrow-targeted thrombopoietin delivery via engineered platelet-derived vesicle-loaded dissolving microneedles for treating ionizing radiation-induced injury |
| title_full | Bone marrow-targeted thrombopoietin delivery via engineered platelet-derived vesicle-loaded dissolving microneedles for treating ionizing radiation-induced injury |
| title_fullStr | Bone marrow-targeted thrombopoietin delivery via engineered platelet-derived vesicle-loaded dissolving microneedles for treating ionizing radiation-induced injury |
| title_full_unstemmed | Bone marrow-targeted thrombopoietin delivery via engineered platelet-derived vesicle-loaded dissolving microneedles for treating ionizing radiation-induced injury |
| title_short | Bone marrow-targeted thrombopoietin delivery via engineered platelet-derived vesicle-loaded dissolving microneedles for treating ionizing radiation-induced injury |
| title_sort | bone marrow targeted thrombopoietin delivery via engineered platelet derived vesicle loaded dissolving microneedles for treating ionizing radiation induced injury |
| topic | Microneedle Activated platelet-derived vesicles Thrombopoietin Ionizing radiation Mitochondria Hematopoietic stem cells |
| url | http://www.sciencedirect.com/science/article/pii/S2590006425005502 |
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