Genetically engineered CXCR4-modified exosomes for delivery of miR-126 mimics to macrophages alleviate periodontitis
Abstract Biofilm-related diseases are a group of diseases that tolerate antimicrobial chemotherapies and therefore are refractory to treatment. Periodontitis, a non-device chronic biofilm disease induced by dental plaque, can serve as an excellent in vivo model to study the important effects of host...
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| Format: | Article |
| Language: | English |
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BMC
2023-03-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | https://doi.org/10.1186/s12951-023-01863-w |
| _version_ | 1797853599695372288 |
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| author | Haotian Luo Danying Chen Ruoyu Li Runze Li Yungshan Teng Yang Cao Xuenong Zou Weicai Wang Chen Zhou |
| author_facet | Haotian Luo Danying Chen Ruoyu Li Runze Li Yungshan Teng Yang Cao Xuenong Zou Weicai Wang Chen Zhou |
| author_sort | Haotian Luo |
| collection | DOAJ |
| description | Abstract Biofilm-related diseases are a group of diseases that tolerate antimicrobial chemotherapies and therefore are refractory to treatment. Periodontitis, a non-device chronic biofilm disease induced by dental plaque, can serve as an excellent in vivo model to study the important effects of host factors on the biofilm microenvironment. Macrophage activity is one of the key factors that modulate the progression of inflammation-driven destruction in periodontitis; therefore it is an important host immunomodulatory factor. In this study, the reduction of microRNA-126 (miR-126) with the recruitment of macrophages in periodontitis was confirmed in clinical samples, and a strategy for targeted delivery of miR-126 to macrophages was explored. Exosomes overexpressing the C-X-C motif chemokine receptor 4 (CXCR4) loaded with miR-126 (CXCR4-miR126-Exo) was successfully constructed, which reduced off-target delivery to macrophages and regulated macrophages toward the anti-inflammatory phenotype. In vivo local injection of CXCR4-miR126-Exo into sites of periodontitis in rats effectively reduced bone resorption and osteoclastogenesis and inhibited the progression of periodontitis. These results provide new insights for designing novel immunomodulatory factor targeted delivery systems to treat periodontitis and other biofilm-related diseases. |
| first_indexed | 2024-04-09T19:53:21Z |
| format | Article |
| id | doaj.art-a365c2f790294f8fbeaae265291b1631 |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-04-09T19:53:21Z |
| publishDate | 2023-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-a365c2f790294f8fbeaae265291b16312023-04-03T05:39:37ZengBMCJournal of Nanobiotechnology1477-31552023-03-0121111510.1186/s12951-023-01863-wGenetically engineered CXCR4-modified exosomes for delivery of miR-126 mimics to macrophages alleviate periodontitisHaotian Luo0Danying Chen1Ruoyu Li2Runze Li3Yungshan Teng4Yang Cao5Xuenong Zou6Weicai Wang7Chen Zhou8Hospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen UniversityHospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen UniversityHospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen UniversityHospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen UniversityHospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen UniversityHospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen UniversityGuangdong Provincial Key Laboratory of Orthopaedics and Traumatology, Department of Spine Surgery, The First Affiliated Hospital, Sun Yat-sen UniversityHospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen UniversityHospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen UniversityAbstract Biofilm-related diseases are a group of diseases that tolerate antimicrobial chemotherapies and therefore are refractory to treatment. Periodontitis, a non-device chronic biofilm disease induced by dental plaque, can serve as an excellent in vivo model to study the important effects of host factors on the biofilm microenvironment. Macrophage activity is one of the key factors that modulate the progression of inflammation-driven destruction in periodontitis; therefore it is an important host immunomodulatory factor. In this study, the reduction of microRNA-126 (miR-126) with the recruitment of macrophages in periodontitis was confirmed in clinical samples, and a strategy for targeted delivery of miR-126 to macrophages was explored. Exosomes overexpressing the C-X-C motif chemokine receptor 4 (CXCR4) loaded with miR-126 (CXCR4-miR126-Exo) was successfully constructed, which reduced off-target delivery to macrophages and regulated macrophages toward the anti-inflammatory phenotype. In vivo local injection of CXCR4-miR126-Exo into sites of periodontitis in rats effectively reduced bone resorption and osteoclastogenesis and inhibited the progression of periodontitis. These results provide new insights for designing novel immunomodulatory factor targeted delivery systems to treat periodontitis and other biofilm-related diseases.https://doi.org/10.1186/s12951-023-01863-wBiofilm diseasesTargeted deliveryImmunomodulationGene therapyExtracellular vesicles |
| spellingShingle | Haotian Luo Danying Chen Ruoyu Li Runze Li Yungshan Teng Yang Cao Xuenong Zou Weicai Wang Chen Zhou Genetically engineered CXCR4-modified exosomes for delivery of miR-126 mimics to macrophages alleviate periodontitis Journal of Nanobiotechnology Biofilm diseases Targeted delivery Immunomodulation Gene therapy Extracellular vesicles |
| title | Genetically engineered CXCR4-modified exosomes for delivery of miR-126 mimics to macrophages alleviate periodontitis |
| title_full | Genetically engineered CXCR4-modified exosomes for delivery of miR-126 mimics to macrophages alleviate periodontitis |
| title_fullStr | Genetically engineered CXCR4-modified exosomes for delivery of miR-126 mimics to macrophages alleviate periodontitis |
| title_full_unstemmed | Genetically engineered CXCR4-modified exosomes for delivery of miR-126 mimics to macrophages alleviate periodontitis |
| title_short | Genetically engineered CXCR4-modified exosomes for delivery of miR-126 mimics to macrophages alleviate periodontitis |
| title_sort | genetically engineered cxcr4 modified exosomes for delivery of mir 126 mimics to macrophages alleviate periodontitis |
| topic | Biofilm diseases Targeted delivery Immunomodulation Gene therapy Extracellular vesicles |
| url | https://doi.org/10.1186/s12951-023-01863-w |
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