Direct Delivery of Apatite Nanoparticle-Encapsulated siRNA Targeting TIMP-1 for Intractable Abnormal Scars
Hypertrophic scars (HSs) and keloids are histologically characterized by excessive extracellular matrix (ECM) deposition. ECM deposition depends on the balance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteases (TIMPs). TIMP-1 has been linked to ECM degradation and is...
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| Format: | Article |
| Language: | English |
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Elsevier
2020-12-01
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| Series: | Molecular Therapy: Nucleic Acids |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253120302341 |
| _version_ | 1818448634200457216 |
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| author | Masayo Aoki Noriko M. Matsumoto Teruyuki Dohi Hiroaki Kuwahawa Satoshi Akaishi Yuri Okubo Rei Ogawa Hirofumi Yamamoto Kazuaki Takabe |
| author_facet | Masayo Aoki Noriko M. Matsumoto Teruyuki Dohi Hiroaki Kuwahawa Satoshi Akaishi Yuri Okubo Rei Ogawa Hirofumi Yamamoto Kazuaki Takabe |
| author_sort | Masayo Aoki |
| collection | DOAJ |
| description | Hypertrophic scars (HSs) and keloids are histologically characterized by excessive extracellular matrix (ECM) deposition. ECM deposition depends on the balance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteases (TIMPs). TIMP-1 has been linked to ECM degradation and is therefore a promising therapeutic strategy. In this study, we generated super carbonate apatite (sCA) nanoparticle-encapsulated TIMP-1 small interfering RNA (siRNA) (siTIMP1) preparations and examined the effect of local injections on mouse HSs and on ex vivo-cultured keloids. The sCA-siTIMP1 injections significantly reduced scar formation, scar cross-sectional areas, collagen densities, and collagen types I and III levels in the lesions. None of the mice died or exhibited abnormal endpoints. Apatite accumulation was not detected in the other organs. In an ex vivo keloid tissue culture system, sCA-siTIMP1 injections reduced the thickness and complexity of collagen bundles. Our results showed that topical sCA-siTIMP1 injections during mechanical stress-induced HS development reduced scar size. When keloids were injected three times with sCA-siTIMP1 during 6 days, keloidal collagen levels decreased substantially. Accordingly, sCA-siRNA delivery may be an effective approach for keloid treatment, and further investigations are needed to enable its practical use. |
| first_indexed | 2024-12-14T20:22:38Z |
| format | Article |
| id | doaj.art-47ed67e23cb14037a04208737e40f96e |
| institution | Directory Open Access Journal |
| issn | 2162-2531 |
| language | English |
| last_indexed | 2024-12-14T20:22:38Z |
| publishDate | 2020-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj.art-47ed67e23cb14037a04208737e40f96e2022-12-21T22:48:41ZengElsevierMolecular Therapy: Nucleic Acids2162-25312020-12-01225061Direct Delivery of Apatite Nanoparticle-Encapsulated siRNA Targeting TIMP-1 for Intractable Abnormal ScarsMasayo Aoki0Noriko M. Matsumoto1Teruyuki Dohi2Hiroaki Kuwahawa3Satoshi Akaishi4Yuri Okubo5Rei Ogawa6Hirofumi Yamamoto7Kazuaki Takabe8Department of Plastic, Reconstructive, and Aesthetic Surgery, Nippon Medical School, Tokyo 113-8603, Japan; Department of Biochemistry and Molecular Biology, Nippon Medical School, Tokyo, Japan; Corresponding author: Masayo Aoki, Department of Plastic, Reconstructive, and Aesthetic Surgery, Nippon Medical School, 1-1-5 Sendagi, Bunkyo, Tokyo 113-8603, Japan.Department of Plastic, Reconstructive, and Aesthetic Surgery, Nippon Medical School, Tokyo 113-8603, JapanDepartment of Plastic, Reconstructive, and Aesthetic Surgery, Nippon Medical School, Tokyo 113-8603, JapanDepartment of Plastic and Reconstructive Surgery, Nippon Medical School Musashi Kosugi Hospital, Kanagawa, JapanDepartment of Plastic and Reconstructive Surgery, Nippon Medical School Musashi Kosugi Hospital, Kanagawa, JapanDepartment of Plastic, Reconstructive, and Aesthetic Surgery, Nippon Medical School, Tokyo 113-8603, JapanDepartment of Plastic, Reconstructive, and Aesthetic Surgery, Nippon Medical School, Tokyo 113-8603, JapanDepartment of Molecular Pathology, Osaka University, Osaka, JapanDivision of Breast Surgery, Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA; Department of Surgery, University at Buffalo Jacob School of Medicine and Biomedical Sciences, The State University of New York, Buffalo, NY, USAHypertrophic scars (HSs) and keloids are histologically characterized by excessive extracellular matrix (ECM) deposition. ECM deposition depends on the balance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteases (TIMPs). TIMP-1 has been linked to ECM degradation and is therefore a promising therapeutic strategy. In this study, we generated super carbonate apatite (sCA) nanoparticle-encapsulated TIMP-1 small interfering RNA (siRNA) (siTIMP1) preparations and examined the effect of local injections on mouse HSs and on ex vivo-cultured keloids. The sCA-siTIMP1 injections significantly reduced scar formation, scar cross-sectional areas, collagen densities, and collagen types I and III levels in the lesions. None of the mice died or exhibited abnormal endpoints. Apatite accumulation was not detected in the other organs. In an ex vivo keloid tissue culture system, sCA-siTIMP1 injections reduced the thickness and complexity of collagen bundles. Our results showed that topical sCA-siTIMP1 injections during mechanical stress-induced HS development reduced scar size. When keloids were injected three times with sCA-siTIMP1 during 6 days, keloidal collagen levels decreased substantially. Accordingly, sCA-siRNA delivery may be an effective approach for keloid treatment, and further investigations are needed to enable its practical use.http://www.sciencedirect.com/science/article/pii/S2162253120302341abnormal scarkeloidhyprtrophic scarsiRNAnanoparticleTIMP |
| spellingShingle | Masayo Aoki Noriko M. Matsumoto Teruyuki Dohi Hiroaki Kuwahawa Satoshi Akaishi Yuri Okubo Rei Ogawa Hirofumi Yamamoto Kazuaki Takabe Direct Delivery of Apatite Nanoparticle-Encapsulated siRNA Targeting TIMP-1 for Intractable Abnormal Scars Molecular Therapy: Nucleic Acids abnormal scar keloid hyprtrophic scar siRNA nanoparticle TIMP |
| title | Direct Delivery of Apatite Nanoparticle-Encapsulated siRNA Targeting TIMP-1 for Intractable Abnormal Scars |
| title_full | Direct Delivery of Apatite Nanoparticle-Encapsulated siRNA Targeting TIMP-1 for Intractable Abnormal Scars |
| title_fullStr | Direct Delivery of Apatite Nanoparticle-Encapsulated siRNA Targeting TIMP-1 for Intractable Abnormal Scars |
| title_full_unstemmed | Direct Delivery of Apatite Nanoparticle-Encapsulated siRNA Targeting TIMP-1 for Intractable Abnormal Scars |
| title_short | Direct Delivery of Apatite Nanoparticle-Encapsulated siRNA Targeting TIMP-1 for Intractable Abnormal Scars |
| title_sort | direct delivery of apatite nanoparticle encapsulated sirna targeting timp 1 for intractable abnormal scars |
| topic | abnormal scar keloid hyprtrophic scar siRNA nanoparticle TIMP |
| url | http://www.sciencedirect.com/science/article/pii/S2162253120302341 |
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