3D-printing magnesium–polycaprolactone loaded with melatonin inhibits the development of osteosarcoma by regulating cell-in-cell structures
Abstract Melatonin has been proposed as a potent anticarcinogen presents a short half-life for osteosarcoma (OS). Cell-in-cell (CIC) structures play a role in the development of malignant tumors by changing the tumor cell energy metabolism. This study developed a melatonin-loaded 3D printed magnesiu...
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| Format: | Article |
| Language: | English |
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BMC
2021-09-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | https://doi.org/10.1186/s12951-021-01012-1 |
| _version_ | 1798024719778185216 |
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| author | Weilin Zhang Wei Zhao Qin Li Duoyi Zhao Junxing Qu Ziyang Yuan Zhihong Cheng Xiaojuan Zhu Xiuli Zhuang Zhiyu Zhang |
| author_facet | Weilin Zhang Wei Zhao Qin Li Duoyi Zhao Junxing Qu Ziyang Yuan Zhihong Cheng Xiaojuan Zhu Xiuli Zhuang Zhiyu Zhang |
| author_sort | Weilin Zhang |
| collection | DOAJ |
| description | Abstract Melatonin has been proposed as a potent anticarcinogen presents a short half-life for osteosarcoma (OS). Cell-in-cell (CIC) structures play a role in the development of malignant tumors by changing the tumor cell energy metabolism. This study developed a melatonin-loaded 3D printed magnesium–polycaprolactone (Mg–PCL) scaffold and investigated its effect and molecular mechanism on CIC in OS. Mg–PCL scaffold was prepared by 3D-printing and its characteristic was determined. The effect and molecular mechanism of Mg–PCL scaffold as well as melatonin-loaded Mg–PCL on OS growth and progression were investigated in vivo and in vitro. We found that melatonin receptor 1 (MT1) and CIC expressions were increased in OS tissues and cells. Melatonin treatment inhibit the key CIC pathway, Rho/ROCK, through the cAMP/PKA signaling pathway, interfering with the mitochondrial physiology of OS cells, and thus playing an anti-invasion and anti-metastasis role in OS. The Mg–PCL–MT could significantly inhibit distant organ metastasis of OS in the in vivo model. Our results showed that melatonin-loaded Mg–PCL scaffolds inhibited the proliferation, invasion and metastasis of OS cells through the CIC pathway. The Mg–PCL–MT could be a potential therapeutics for OS. |
| first_indexed | 2024-04-11T18:07:14Z |
| format | Article |
| id | doaj.art-211ff65cdcd04bae864097d3234adf99 |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-04-11T18:07:14Z |
| publishDate | 2021-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-211ff65cdcd04bae864097d3234adf992022-12-22T04:10:16ZengBMCJournal of Nanobiotechnology1477-31552021-09-0119112010.1186/s12951-021-01012-13D-printing magnesium–polycaprolactone loaded with melatonin inhibits the development of osteosarcoma by regulating cell-in-cell structuresWeilin Zhang0Wei Zhao1Qin Li2Duoyi Zhao3Junxing Qu4Ziyang Yuan5Zhihong Cheng6Xiaojuan Zhu7Xiuli Zhuang8Zhiyu Zhang9Department of Orthopedics, The Fourth Affiliated Hospital of China Medical UniversityDepartment of Orthopedics, The Fourth Affiliated Hospital of China Medical UniversityTranslational Medicine Center, The Fourth Affiliated Hospital of China Medical UniversityDepartment of Orthopedics, The Fourth Affiliated Hospital of China Medical UniversityDepartment of Orthopedics, The Fourth Affiliated Hospital of China Medical UniversityDepartment of Orthopedics, The Fourth Affiliated Hospital of China Medical UniversityDepartment of Orthopedics, The Fourth Affiliated Hospital of China Medical UniversityKey Laboratory of Molecular Epigenetics, Ministry of Education and Institute of Cytology and Genetics, Northeast Normal UniversityKey Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry Chinese Academy of SciencesDepartment of Orthopedics, The Fourth Affiliated Hospital of China Medical UniversityAbstract Melatonin has been proposed as a potent anticarcinogen presents a short half-life for osteosarcoma (OS). Cell-in-cell (CIC) structures play a role in the development of malignant tumors by changing the tumor cell energy metabolism. This study developed a melatonin-loaded 3D printed magnesium–polycaprolactone (Mg–PCL) scaffold and investigated its effect and molecular mechanism on CIC in OS. Mg–PCL scaffold was prepared by 3D-printing and its characteristic was determined. The effect and molecular mechanism of Mg–PCL scaffold as well as melatonin-loaded Mg–PCL on OS growth and progression were investigated in vivo and in vitro. We found that melatonin receptor 1 (MT1) and CIC expressions were increased in OS tissues and cells. Melatonin treatment inhibit the key CIC pathway, Rho/ROCK, through the cAMP/PKA signaling pathway, interfering with the mitochondrial physiology of OS cells, and thus playing an anti-invasion and anti-metastasis role in OS. The Mg–PCL–MT could significantly inhibit distant organ metastasis of OS in the in vivo model. Our results showed that melatonin-loaded Mg–PCL scaffolds inhibited the proliferation, invasion and metastasis of OS cells through the CIC pathway. The Mg–PCL–MT could be a potential therapeutics for OS.https://doi.org/10.1186/s12951-021-01012-1OsteosarcomaMelatoninCell-in-cellMg–PCLRho/ROCKcAMP/PKA signaling pathway |
| spellingShingle | Weilin Zhang Wei Zhao Qin Li Duoyi Zhao Junxing Qu Ziyang Yuan Zhihong Cheng Xiaojuan Zhu Xiuli Zhuang Zhiyu Zhang 3D-printing magnesium–polycaprolactone loaded with melatonin inhibits the development of osteosarcoma by regulating cell-in-cell structures Journal of Nanobiotechnology Osteosarcoma Melatonin Cell-in-cell Mg–PCL Rho/ROCK cAMP/PKA signaling pathway |
| title | 3D-printing magnesium–polycaprolactone loaded with melatonin inhibits the development of osteosarcoma by regulating cell-in-cell structures |
| title_full | 3D-printing magnesium–polycaprolactone loaded with melatonin inhibits the development of osteosarcoma by regulating cell-in-cell structures |
| title_fullStr | 3D-printing magnesium–polycaprolactone loaded with melatonin inhibits the development of osteosarcoma by regulating cell-in-cell structures |
| title_full_unstemmed | 3D-printing magnesium–polycaprolactone loaded with melatonin inhibits the development of osteosarcoma by regulating cell-in-cell structures |
| title_short | 3D-printing magnesium–polycaprolactone loaded with melatonin inhibits the development of osteosarcoma by regulating cell-in-cell structures |
| title_sort | 3d printing magnesium polycaprolactone loaded with melatonin inhibits the development of osteosarcoma by regulating cell in cell structures |
| topic | Osteosarcoma Melatonin Cell-in-cell Mg–PCL Rho/ROCK cAMP/PKA signaling pathway |
| url | https://doi.org/10.1186/s12951-021-01012-1 |
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