Precise Diabetic Wound Therapy: PLS Nanospheres Eliminate Senescent Cells via DPP4 Targeting and PARP1 Activation
Abstract Diabetic ulcers, a difficult problem faced by clinicians, are strongly associated with an increase in cellular senescence. Few empirical studies have focused on exploring a targeted strategy to cure diabetic wounds by eliminating senescent fibroblasts (SFs) and reducing side effects. In thi...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-01-01
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| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202104128 |
| _version_ | 1798034157180289024 |
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| author | Renliang Zhao Xiangyun Jin Ang Li Bitong Xu Yifan Shen Wei Wang Jinghuan Huang Yadong Zhang Xiaolin Li |
| author_facet | Renliang Zhao Xiangyun Jin Ang Li Bitong Xu Yifan Shen Wei Wang Jinghuan Huang Yadong Zhang Xiaolin Li |
| author_sort | Renliang Zhao |
| collection | DOAJ |
| description | Abstract Diabetic ulcers, a difficult problem faced by clinicians, are strongly associated with an increase in cellular senescence. Few empirical studies have focused on exploring a targeted strategy to cure diabetic wounds by eliminating senescent fibroblasts (SFs) and reducing side effects. In this study, poly‐l‐lysine/sodium alginate (PLS) is modified with talabostat (PT100) and encapsulates a PARP1 plasmid (PARP1@PLS‐PT100) for delivery to target the dipeptidyl peptidase 4 (DPP4) receptor and eliminate SFs. PARP1@PLS‐PT100 releases encapsulated plasmids, displaying high selectivity for SFs over normal fibroblasts by targeting the DPP4 receptor, decreasing senescence‐associated secretory phenotypes (SASPs), and stimulating the secretion of anti‐inflammatory factors. Furthermore, the increased apoptosis of SFs and the disappearance of cellular senescence alleviates SASPs, accelerates re‐epithelialization and collagen deposition, and significantly induces macrophage M2 polarization, which mediates tissue repair and the inflammatory response. This innovative strategy has revealed the previously undefined role of PARP1@PLS‐PT100 in promoting diabetic wound healing, suggesting its therapeutic potential in refractory wound repair. |
| first_indexed | 2024-04-11T20:39:27Z |
| format | Article |
| id | doaj.art-0846996c15ad4d46a9f464925d72e600 |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-04-11T20:39:27Z |
| publishDate | 2022-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-0846996c15ad4d46a9f464925d72e6002022-12-22T04:04:14ZengWileyAdvanced Science2198-38442022-01-0191n/an/a10.1002/advs.202104128Precise Diabetic Wound Therapy: PLS Nanospheres Eliminate Senescent Cells via DPP4 Targeting and PARP1 ActivationRenliang Zhao0Xiangyun Jin1Ang Li2Bitong Xu3Yifan Shen4Wei Wang5Jinghuan Huang6Yadong Zhang7Xiaolin Li8Department of Orthopedic Surgery and Shanghai Institute of Microsurgery on Extremities Shanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai 200233 ChinaDepartment of Orthopedic Trauma Renji Hospital School of Medicine Shanghai Jiao Tong University Shanghai 200127 P. R. ChinaDepartment of Orthopedic Surgery and Shanghai Institute of Microsurgery on Extremities Shanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai 200233 ChinaDepartment of Spine Center for Orthopaedic Surgery The Third Affiliated Hospital of Southern Medical University Guangzhou 510515 ChinaDepartment of Orthopedic Surgery and Shanghai Institute of Microsurgery on Extremities Shanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai 200233 ChinaDepartment of Orthopedic Surgery and Shanghai Institute of Microsurgery on Extremities Shanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai 200233 ChinaDepartment of Orthopedic Surgery and Shanghai Institute of Microsurgery on Extremities Shanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai 200233 ChinaDepartment of Spine Center for Orthopaedic Surgery The Third Affiliated Hospital of Southern Medical University Guangzhou 510515 ChinaDepartment of Orthopedic Surgery and Shanghai Institute of Microsurgery on Extremities Shanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai 200233 ChinaAbstract Diabetic ulcers, a difficult problem faced by clinicians, are strongly associated with an increase in cellular senescence. Few empirical studies have focused on exploring a targeted strategy to cure diabetic wounds by eliminating senescent fibroblasts (SFs) and reducing side effects. In this study, poly‐l‐lysine/sodium alginate (PLS) is modified with talabostat (PT100) and encapsulates a PARP1 plasmid (PARP1@PLS‐PT100) for delivery to target the dipeptidyl peptidase 4 (DPP4) receptor and eliminate SFs. PARP1@PLS‐PT100 releases encapsulated plasmids, displaying high selectivity for SFs over normal fibroblasts by targeting the DPP4 receptor, decreasing senescence‐associated secretory phenotypes (SASPs), and stimulating the secretion of anti‐inflammatory factors. Furthermore, the increased apoptosis of SFs and the disappearance of cellular senescence alleviates SASPs, accelerates re‐epithelialization and collagen deposition, and significantly induces macrophage M2 polarization, which mediates tissue repair and the inflammatory response. This innovative strategy has revealed the previously undefined role of PARP1@PLS‐PT100 in promoting diabetic wound healing, suggesting its therapeutic potential in refractory wound repair.https://doi.org/10.1002/advs.202104128diabetic wound healingDPP4 receptornanospheresselective targetingsenescence |
| spellingShingle | Renliang Zhao Xiangyun Jin Ang Li Bitong Xu Yifan Shen Wei Wang Jinghuan Huang Yadong Zhang Xiaolin Li Precise Diabetic Wound Therapy: PLS Nanospheres Eliminate Senescent Cells via DPP4 Targeting and PARP1 Activation Advanced Science diabetic wound healing DPP4 receptor nanospheres selective targeting senescence |
| title | Precise Diabetic Wound Therapy: PLS Nanospheres Eliminate Senescent Cells via DPP4 Targeting and PARP1 Activation |
| title_full | Precise Diabetic Wound Therapy: PLS Nanospheres Eliminate Senescent Cells via DPP4 Targeting and PARP1 Activation |
| title_fullStr | Precise Diabetic Wound Therapy: PLS Nanospheres Eliminate Senescent Cells via DPP4 Targeting and PARP1 Activation |
| title_full_unstemmed | Precise Diabetic Wound Therapy: PLS Nanospheres Eliminate Senescent Cells via DPP4 Targeting and PARP1 Activation |
| title_short | Precise Diabetic Wound Therapy: PLS Nanospheres Eliminate Senescent Cells via DPP4 Targeting and PARP1 Activation |
| title_sort | precise diabetic wound therapy pls nanospheres eliminate senescent cells via dpp4 targeting and parp1 activation |
| topic | diabetic wound healing DPP4 receptor nanospheres selective targeting senescence |
| url | https://doi.org/10.1002/advs.202104128 |
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