Dual-pathological cascade delivery of apoptotic vesicles for targeted therapy in intervertebral disc degeneration
Achieving effective drug delivery and therapeutic efficacy poses significant challenges in intervertebral disc degeneration (IDD). Here, we developed a dual-pathological cascade delivery system utilizing therapeutic mesenchymal stem cell-derived apoptotic vesicles (ApoVs). These vesicles are enginee...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-10-01
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| Series: | Materials Today Bio |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590006425007707 |
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| author | Wei Chen Tianyuan Zhao Yiming Ren Wenzhe Huang Jiyuan Xia Zhenxin Hu Libo Chen Hao Li Qi Zhang Han Wang Penglei Cui Quanyi Guo Da He |
| author_facet | Wei Chen Tianyuan Zhao Yiming Ren Wenzhe Huang Jiyuan Xia Zhenxin Hu Libo Chen Hao Li Qi Zhang Han Wang Penglei Cui Quanyi Guo Da He |
| author_sort | Wei Chen |
| collection | DOAJ |
| description | Achieving effective drug delivery and therapeutic efficacy poses significant challenges in intervertebral disc degeneration (IDD). Here, we developed a dual-pathological cascade delivery system utilizing therapeutic mesenchymal stem cell-derived apoptotic vesicles (ApoVs). These vesicles are engineered with MMP13-responsive cell-penetrating peptides (MR-ApoVs) for targeted modulation of senescence. A reactive oxygen species (ROS)-responsive hydrogel incorporating CD44 aptamers (Apt-Gel) was developed to provide high-affinity retention and spatiotemporal controlled release of MR-ApoVs. In this system, MR-ApoV release is first triggered by hydrogel degradation in response to elevated ROS levels. Subsequently, the MMP13-responsive peptides on MR-ApoVs are activated to enhance their internalization into senescent nucleus pulposus (NP) cells, thereby achieving a sequential response to pathological signals within the degenerative disc microenvironment. In a rat model of IDD, MR-ApoV@Apt-Gel effectively attenuated NP cell senescence, restored extracellular matrix homeostasis, preserved disc hydration, and maintained intervertebral disc height. This dual-pathological cascade-responsive strategy represents a promising therapeutic approach for IDD treatment. |
| format | Article |
| id | doaj-art-e66fefd72d4249c3951de6861c52bae6 |
| institution | Kabale University |
| issn | 2590-0064 |
| language | English |
| publishDate | 2025-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Materials Today Bio |
| spelling | doaj-art-e66fefd72d4249c3951de6861c52bae62025-08-20T04:02:51ZengElsevierMaterials Today Bio2590-00642025-10-013410220010.1016/j.mtbio.2025.102200Dual-pathological cascade delivery of apoptotic vesicles for targeted therapy in intervertebral disc degenerationWei Chen0Tianyuan Zhao1Yiming Ren2Wenzhe Huang3Jiyuan Xia4Zhenxin Hu5Libo Chen6Hao Li7Qi Zhang8Han Wang9Penglei Cui10Quanyi Guo11Da He12Department of Spine, Peking University Fourth School of Clinical Medicine, Beijing, 100035, ChinaDepartment of Orthopedics, Peking University Third Hospital, Beijing, 100191, ChinaInstitute of Orthopedics, Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & War Injuries PLA, Beijing, 100853, ChinaDepartment of Spine, Peking University Fourth School of Clinical Medicine, Beijing, 100035, ChinaDepartment of Spine, Beijing Jishuitan Hospital Affiliated to Capital Medical University, Beijing, 100035, ChinaDepartment of Spine, Peking University Fourth School of Clinical Medicine, Beijing, 100035, ChinaInstitute of Orthopedics, Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & War Injuries PLA, Beijing, 100853, ChinaInstitute of Orthopedics, Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & War Injuries PLA, Beijing, 100853, ChinaDepartment of Spine, Beijing Jishuitan Hospital Affiliated to Capital Medical University, Beijing, 100035, ChinaDepartment of Spine, Beijing Jishuitan Hospital Affiliated to Capital Medical University, Beijing, 100035, ChinaDepartment of Spine, Beijing Jishuitan Hospital Affiliated to Capital Medical University, Beijing, 100035, China; Corresponding author. Department of Spine, Beijing Jishuitan Hospital, Capital Medical University, Beijing, 100035, China.Institute of Orthopedics, Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & War Injuries PLA, Beijing, 100853, China; Corresponding author. Institute of Orthopedics, Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & War Injuries PLA, Beijing, 100853, China.Department of Spine, Peking University Fourth School of Clinical Medicine, Beijing, 100035, China; Corresponding author. Department of Spine, Peking University Fourth School of Clinical Medicine, Beijing, 100035, China.Achieving effective drug delivery and therapeutic efficacy poses significant challenges in intervertebral disc degeneration (IDD). Here, we developed a dual-pathological cascade delivery system utilizing therapeutic mesenchymal stem cell-derived apoptotic vesicles (ApoVs). These vesicles are engineered with MMP13-responsive cell-penetrating peptides (MR-ApoVs) for targeted modulation of senescence. A reactive oxygen species (ROS)-responsive hydrogel incorporating CD44 aptamers (Apt-Gel) was developed to provide high-affinity retention and spatiotemporal controlled release of MR-ApoVs. In this system, MR-ApoV release is first triggered by hydrogel degradation in response to elevated ROS levels. Subsequently, the MMP13-responsive peptides on MR-ApoVs are activated to enhance their internalization into senescent nucleus pulposus (NP) cells, thereby achieving a sequential response to pathological signals within the degenerative disc microenvironment. In a rat model of IDD, MR-ApoV@Apt-Gel effectively attenuated NP cell senescence, restored extracellular matrix homeostasis, preserved disc hydration, and maintained intervertebral disc height. This dual-pathological cascade-responsive strategy represents a promising therapeutic approach for IDD treatment.http://www.sciencedirect.com/science/article/pii/S2590006425007707Apoptotic vesiclesAptamerHydrogelCellular senescenceIntervertebral disc degeneration |
| spellingShingle | Wei Chen Tianyuan Zhao Yiming Ren Wenzhe Huang Jiyuan Xia Zhenxin Hu Libo Chen Hao Li Qi Zhang Han Wang Penglei Cui Quanyi Guo Da He Dual-pathological cascade delivery of apoptotic vesicles for targeted therapy in intervertebral disc degeneration Materials Today Bio Apoptotic vesicles Aptamer Hydrogel Cellular senescence Intervertebral disc degeneration |
| title | Dual-pathological cascade delivery of apoptotic vesicles for targeted therapy in intervertebral disc degeneration |
| title_full | Dual-pathological cascade delivery of apoptotic vesicles for targeted therapy in intervertebral disc degeneration |
| title_fullStr | Dual-pathological cascade delivery of apoptotic vesicles for targeted therapy in intervertebral disc degeneration |
| title_full_unstemmed | Dual-pathological cascade delivery of apoptotic vesicles for targeted therapy in intervertebral disc degeneration |
| title_short | Dual-pathological cascade delivery of apoptotic vesicles for targeted therapy in intervertebral disc degeneration |
| title_sort | dual pathological cascade delivery of apoptotic vesicles for targeted therapy in intervertebral disc degeneration |
| topic | Apoptotic vesicles Aptamer Hydrogel Cellular senescence Intervertebral disc degeneration |
| url | http://www.sciencedirect.com/science/article/pii/S2590006425007707 |
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