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Nitrogen-containing bisphosphonate-loaded micro-arc oxidation coating for biodegradable magnesium alloy pellets inhibits osteosarcoma through targeting of the mevalonate pathway
Li, Mei1; Yao, Mengyu2,3; Wang, Weidan4; Wan, Peng5; Chu, Xiao1; Zheng, Yufeng6; Yang, Ke7; Zhang, Yu1
Corresponding AuthorWan, Peng(wanpeng@dgut.edu.cn) ; Zhang, Yu(luck_2001@126.com)
2021-02-01
Source PublicationACTA BIOMATERIALIA
ISSN1742-7061
Volume121Pages:682-694
AbstractOsteosarcoma (OS) remains one of the most threatening primary malignant human tumors of the bone, especially in the first or second decade of life. Unfortunately, the clinical therapeutic efficacy has not substantially improved over the past four decades. Therefore, to achieve efficient tumor eradication, a new approach to prevent tumor recurrence is urgently needed. Here, we develop a new bisphosphonate (BP)-loaded microarc oxidation (MAO) coated magnesium-strontium (Mg-Sr) alloy pellet that can inhibit OS, and we illuminate the cellular and molecular mechanisms of the inhibiting effect. To generate such pellets, nitrogen-containing BP is chemically conjugated with a MAO coating on hollow Mg-Sr alloys. We demonstrate that BP coated Mg pellet has multiple desired features for OS therapy through in vitro and in vivo studies. At the cellular level, BP coated Mg pellets not only induce apoptosis and necrosis, as well as antitumor invasion of OS cells in the two-dimensional (2D) cell culture environment, but also damage the formation of multicellular tumor spheroids by OS cell lines in the three-dimensional (3D) cell culture environment. At the in vivo level, BP coated Mg pellets can destroy tumors and prevent neoplasm recurrence via synergistic Mg degradation and drug release. It is further suggested that the superior inhibitory effect on OS of our pellet is achieved by inhibiting the mevalonate pathway at the molecular level. Hence, these results collectively show that the BP coated Mg pellet is a promising candidate for future applications in repairing defects after tumor removal in OS therapy. Statement of significance Osteosarcoma (OS) is prone to metastases and unfavorable prognosis and the clinical therapeutic efficacy has not substantially improved over the past four decades. It is of high demand in developing new materials that can not only repair the bone defects but also inhibit OS in the lesion location. To solve these problems, we design a hollow Mg-Sr alloy pellet that is modificated with micro-arc oxidation coating and then loaded with Bisphosphonates (BP). Our results of the in vitro and in vivo biological assays show the inhibition effects and the corresponding signal pathway of BP coated Mg pellets on OS. Our work illustrates the process and mechanism of the tumor therapeutic efficacy for a new biomaterial, which could expand our understanding the ultimate principle of biomaterials-induced tumor therapy. (c) 2020 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
KeywordMagnesium alloy pellets Bisphosphonates coating Osteosarcoma Multicellular spheroids model Mevalonate pathway
Funding OrganizationNatural Science Foundation of Guangdong Province, China ; National Key Research Program of China ; National Natural Science Foundation of China ; Scientific and Technological Projects of Guangzhou, China ; DGUT
DOI10.1016/j.actbio.2020.11.019
Indexed BySCI
Language英语
Funding ProjectNatural Science Foundation of Guangdong Province, China[2020A1515011447] ; National Key Research Program of China[2017YFB0702604] ; National Natural Science Foundation of China[31771038] ; Scientific and Technological Projects of Guangzhou, China[202002030283] ; DGUT[GC300501-082]
WOS Research AreaEngineering ; Materials Science
WOS SubjectEngineering, Biomedical ; Materials Science, Biomaterials
WOS IDWOS:000614487800005
PublisherELSEVIER SCI LTD
Citation statistics
Document Type期刊论文
Identifierhttp://ir.imr.ac.cn/handle/321006/159154
Collection中国科学院金属研究所
Corresponding AuthorWan, Peng; Zhang, Yu
Affiliation1.Guangdong Acad Med Sci, Guangdong Prov Peoples Hosp, Res Ctr Med Sci, Dept Orthoped, Guangzhou 510080, Peoples R China
2.South China Univ Technol, Sch Mat Sci & Engn, Dept Biomed Engn, Guangzhou 510006, Peoples R China
3.South China Univ Technol, Natl Engn Res Ctr Tissue Restorat & Reconstruct, Guangzhou 510006, Peoples R China
4.Dalian Univ, Dept Orthopaed, Affiliated Zhongshan Hosp, Dalian 116001, Peoples R China
5.Dongguan Univ Technol, Sch Mat Sci & Engn, Dongguan 523808, Peoples R China
6.Peking Univ, Coll Engn, Dept Mat Sci & Engn, Beijing 100871, Peoples R China
7.Chinese Acad Sci, Inst Met Res, Shenyang 110016, Peoples R China
Recommended Citation
GB/T 7714
Li, Mei,Yao, Mengyu,Wang, Weidan,et al. Nitrogen-containing bisphosphonate-loaded micro-arc oxidation coating for biodegradable magnesium alloy pellets inhibits osteosarcoma through targeting of the mevalonate pathway[J]. ACTA BIOMATERIALIA,2021,121:682-694.
APA Li, Mei.,Yao, Mengyu.,Wang, Weidan.,Wan, Peng.,Chu, Xiao.,...&Zhang, Yu.(2021).Nitrogen-containing bisphosphonate-loaded micro-arc oxidation coating for biodegradable magnesium alloy pellets inhibits osteosarcoma through targeting of the mevalonate pathway.ACTA BIOMATERIALIA,121,682-694.
MLA Li, Mei,et al."Nitrogen-containing bisphosphonate-loaded micro-arc oxidation coating for biodegradable magnesium alloy pellets inhibits osteosarcoma through targeting of the mevalonate pathway".ACTA BIOMATERIALIA 121(2021):682-694.
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