Silica nanocarrier-mediated intracellular delivery of rapamycin promotes autophagy-mediated M2 macrophage polarization to regulate bone regeneration
Targeting macrophages to regulate the immune microenvironment is a new strategy for bone regeneration with nano-drugs. Nano-drugs have achieved surprising anti-inflammatory and bone-regenerative effects, however, their underlying mechanisms in macrophages remain to be clarified. Macrophage polarizat...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-06-01
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| Series: | Materials Today Bio |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590006423000832 |
| _version_ | 1797796381202579456 |
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| author | Qing Zhang Mengyu Xin Shuang Yang Qiuyu Wu Xi Xiang Tianqi Wang Wen Zhong Marco N. Helder Richard T. Jaspers Janak Lal Pathak Yin Xiao |
| author_facet | Qing Zhang Mengyu Xin Shuang Yang Qiuyu Wu Xi Xiang Tianqi Wang Wen Zhong Marco N. Helder Richard T. Jaspers Janak Lal Pathak Yin Xiao |
| author_sort | Qing Zhang |
| collection | DOAJ |
| description | Targeting macrophages to regulate the immune microenvironment is a new strategy for bone regeneration with nano-drugs. Nano-drugs have achieved surprising anti-inflammatory and bone-regenerative effects, however, their underlying mechanisms in macrophages remain to be clarified. Macrophage polarization, immunomodulation, and osteogenesis are governed by autophagy. Rapamycin, an autophagy inducer, has shown promising results in bone regeneration, but high dose-mediated cytotoxicity and low bioavailability hinder its clinical application. This study aimed to develop rapamycin-loaded virus-like hollow silica nanoparticles (R@HSNs) which are easily phagocytosed by macrophages and translocated to lysosomes. R@HSNs induced macrophage autophagy, promoted M2 polarization, and alleviated the degree of M1 polarization as indicated by the downregulation of inflammatory factors IL-6, IL-1β, TNF-α, and iNOS, and upregulation of anti-inflammatory factors CD163, CD206, IL-1ra, IL-10, and TGF-β. These effects were nullified by cytochalasin B-induced inhibition of R@HSNs uptake in macrophages. The conditioned medium (CM) collected from R@HSNs-treated macrophages promoted osteogenic differentiation of mouse bone marrow mesenchymal stromal cells (mBMSCs). In a mouse calvaria defect model, free rapamycin treatment was inhibited, but R@HSNs robustly promoted bone defect healing. In conclusion, silica nanocarrier-mediated intracellular rapamycin delivery to macrophages effectively triggers autophagy-mediated M2 macrophage polarization, further enhancing bone regeneration by triggering osteogenic differentiation of mBMSCs. |
| first_indexed | 2024-03-13T03:32:13Z |
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| id | doaj.art-4161c38f27804db780535f5e9bcaeeb3 |
| institution | Directory Open Access Journal |
| issn | 2590-0064 |
| language | English |
| last_indexed | 2024-03-13T03:32:13Z |
| publishDate | 2023-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Materials Today Bio |
| spelling | doaj.art-4161c38f27804db780535f5e9bcaeeb32023-06-24T05:18:33ZengElsevierMaterials Today Bio2590-00642023-06-0120100623Silica nanocarrier-mediated intracellular delivery of rapamycin promotes autophagy-mediated M2 macrophage polarization to regulate bone regenerationQing Zhang0Mengyu Xin1Shuang Yang2Qiuyu Wu3Xi Xiang4Tianqi Wang5Wen Zhong6Marco N. Helder7Richard T. Jaspers8Janak Lal Pathak9Yin Xiao10Affiliated Stomatology Hospital of Guangzhou Medical University, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou 510182, China; Laboratory for Myology, Department of Human Movement Sciences, Faculty of Behavioural and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, 1081 BT Amsterdam, the NetherlandsAffiliated Stomatology Hospital of Guangzhou Medical University, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou 510182, ChinaAffiliated Stomatology Hospital of Guangzhou Medical University, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou 510182, ChinaAffiliated Stomatology Hospital of Guangzhou Medical University, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou 510182, ChinaAffiliated Stomatology Hospital of Guangzhou Medical University, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou 510182, ChinaAffiliated Stomatology Hospital of Guangzhou Medical University, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou 510182, ChinaAffiliated Stomatology Hospital of Guangzhou Medical University, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou 510182, ChinaDepartment of Oral and Maxillofacial Surgery/Oral Pathology, Amsterdam University Medical Centers and Academic Centre for Dentistry Amsterdam (ACTA), Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, 1081 HV Amsterdam, the NetherlandsAffiliated Stomatology Hospital of Guangzhou Medical University, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou 510182, China; Laboratory for Myology, Department of Human Movement Sciences, Faculty of Behavioural and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, 1081 BT Amsterdam, the NetherlandsAffiliated Stomatology Hospital of Guangzhou Medical University, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou 510182, China; Corresponding author.Affiliated Stomatology Hospital of Guangzhou Medical University, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou 510182, China; School of Medicine and Dentistry & Menzies Health Institute Queensland, Griffith University, Gold Coast, QLD 4222, Australia; The Australia-China Centre for Tissue Engineering and Regenerative Medicine (ACCTERM), Queensland University of Technology, Brisbane, QLD 4000, Australia; Corresponding author. Affiliated Stomatology Hospital of Guangzhou Medical University, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou 510182, China.Targeting macrophages to regulate the immune microenvironment is a new strategy for bone regeneration with nano-drugs. Nano-drugs have achieved surprising anti-inflammatory and bone-regenerative effects, however, their underlying mechanisms in macrophages remain to be clarified. Macrophage polarization, immunomodulation, and osteogenesis are governed by autophagy. Rapamycin, an autophagy inducer, has shown promising results in bone regeneration, but high dose-mediated cytotoxicity and low bioavailability hinder its clinical application. This study aimed to develop rapamycin-loaded virus-like hollow silica nanoparticles (R@HSNs) which are easily phagocytosed by macrophages and translocated to lysosomes. R@HSNs induced macrophage autophagy, promoted M2 polarization, and alleviated the degree of M1 polarization as indicated by the downregulation of inflammatory factors IL-6, IL-1β, TNF-α, and iNOS, and upregulation of anti-inflammatory factors CD163, CD206, IL-1ra, IL-10, and TGF-β. These effects were nullified by cytochalasin B-induced inhibition of R@HSNs uptake in macrophages. The conditioned medium (CM) collected from R@HSNs-treated macrophages promoted osteogenic differentiation of mouse bone marrow mesenchymal stromal cells (mBMSCs). In a mouse calvaria defect model, free rapamycin treatment was inhibited, but R@HSNs robustly promoted bone defect healing. In conclusion, silica nanocarrier-mediated intracellular rapamycin delivery to macrophages effectively triggers autophagy-mediated M2 macrophage polarization, further enhancing bone regeneration by triggering osteogenic differentiation of mBMSCs.http://www.sciencedirect.com/science/article/pii/S2590006423000832AutophagyRapamycinHollow silica nanoparticlesMacrophagesOsteogenesis |
| spellingShingle | Qing Zhang Mengyu Xin Shuang Yang Qiuyu Wu Xi Xiang Tianqi Wang Wen Zhong Marco N. Helder Richard T. Jaspers Janak Lal Pathak Yin Xiao Silica nanocarrier-mediated intracellular delivery of rapamycin promotes autophagy-mediated M2 macrophage polarization to regulate bone regeneration Materials Today Bio Autophagy Rapamycin Hollow silica nanoparticles Macrophages Osteogenesis |
| title | Silica nanocarrier-mediated intracellular delivery of rapamycin promotes autophagy-mediated M2 macrophage polarization to regulate bone regeneration |
| title_full | Silica nanocarrier-mediated intracellular delivery of rapamycin promotes autophagy-mediated M2 macrophage polarization to regulate bone regeneration |
| title_fullStr | Silica nanocarrier-mediated intracellular delivery of rapamycin promotes autophagy-mediated M2 macrophage polarization to regulate bone regeneration |
| title_full_unstemmed | Silica nanocarrier-mediated intracellular delivery of rapamycin promotes autophagy-mediated M2 macrophage polarization to regulate bone regeneration |
| title_short | Silica nanocarrier-mediated intracellular delivery of rapamycin promotes autophagy-mediated M2 macrophage polarization to regulate bone regeneration |
| title_sort | silica nanocarrier mediated intracellular delivery of rapamycin promotes autophagy mediated m2 macrophage polarization to regulate bone regeneration |
| topic | Autophagy Rapamycin Hollow silica nanoparticles Macrophages Osteogenesis |
| url | http://www.sciencedirect.com/science/article/pii/S2590006423000832 |
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