Metal-drug nanoparticles-mediated osteolytic microenvironment regulation for enhanced radiotherapy of orthotopic osteosarcoma

doi:10.1016/j.cej.2020.128103

	Metal-drug nanoparticles-mediated osteolytic microenvironment regulation for enhanced radiotherapy of orthotopic osteosarcoma
	Geng, Huan 1; Zhou, Mengxue 2,3; Li, Bin 1; Liu, Liang 1; Yang, Xu 1; Wen, Yinxian 1; Yu, Haijun 5,6; Wang, Hui 4; Chen, Jun 2,3; Chen, Liaobin 1
刊名	CHEMICAL ENGINEERING JOURNAL
	2021-08-01
卷号	417 页码:11
关键词	Metal-drug nanoparticles Orthotopic osteosarcoma Osteolytic microenvironment Zoledronate Radiotherapy
ISSN号	1385-8947
DOI	10.1016/j.cej.2020.128103
通讯作者	Wang, Hui(wanghui19@whu.edu.cn) ; Chen, Jun(chenjun@ihep.ac.cn) ; Chen, Liaobin(lbchen@whu.edu.cn)
英文摘要	Osteosarcoma is the most common primary malignant bone tumor with the pathological essence of osteolysis, which seriously reduces the quality of life. To improve the treatment of osteosarcoma, current strategies focus on inhibiting osteolysis and cancer cell growth through combination therapy. Here, we firstly developed a new "carrier free" core-shell metal-drug nanoparticles to enhance the treatment of orthotopic osteosarcoma through inhibiting osteoclast activity and sensitizing radiotherapy. The core was formed by self-assembly of ferric ions with zoledronate (ZOL). The resultant nanoparticles with active pharmaceutical ingredient (API) content over 60 wt% and changeless ingredients of Fe and ZOL can induce efficient cell death and easy for large-scale synthesis. In addition, the inbuilt ZOL and surface modified hyaluronic acid could make the nanoparticles escape skeleton absorption and increase the concentration of zoledronate at the tumor site. Once accumulated in tumor, the released ZOL attenuated osteoclast activity around the tumors to prevent osteolysis. Meanwhile, the free radicals generated efficiently from HA@FeZOL through Fenton-like reaction sensitized radiotherapy to kill the tumor cells. The results corroborated the feasibility of HA@FeZOL mediated synergistic therapy against orthotopic osteosarcoma through sensitized radiotherapy and osteolysis inhibition. Therefore, this facile nanoplatform provides a new combinatorial strategy for treating osteosarcoma and opens a window for the application of metal-drug nanoparticles.
资助项目	National Natural Science Foundation of China[81972036] ; National Natural Science Foundation of China[81673490] ; National Natural Science Foundation of China[81603214] ; National Natural Science Foundation of China[21574136] ; National Key R&D Program of China[SQ2020YFA080035]
WOS关键词	BISPHOSPHONATES ; ANGIOGENESIS ; CHEMOTHERAPY ; STABILITY ; DESIGN
WOS研究方向	Engineering
语种	英语
出版者	ELSEVIER SCIENCE SA
WOS记录号	WOS:000653229500127
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/297096]
专题	中国科学院上海药物研究所
通讯作者	Wang, Hui; Chen, Jun; Chen, Liaobin
作者单位	1.Wuhan Univ, Dept Orthoped Surg, Zhongnan Hosp, Wuhan 430071, Peoples R China 2.Chinese Acad Sci, Inst High Energy Phys, Multidisciplinary Res Div, CAS Key Lab Biomed Effects Nanomat & Nanosafety, Beijing 100049, Peoples R China 3.Chinese Acad Sci, Univ Chinese Acad Sci UCAS, Beijing 100049, Peoples R China 4.Wuhan Univ, Dept Pharmacol, Hubei Prov Key Lab Dev Originated Dis, Basic Med Sch, Wuhan 430071, Peoples R China 5.Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 6.Chinese Acad Sci, Ctr Pharmaceut, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Geng, Huan,Zhou, Mengxue,Li, Bin,et al. Metal-drug nanoparticles-mediated osteolytic microenvironment regulation for enhanced radiotherapy of orthotopic osteosarcoma[J]. CHEMICAL ENGINEERING JOURNAL,2021,417:11.
APA	Geng, Huan.,Zhou, Mengxue.,Li, Bin.,Liu, Liang.,Yang, Xu.,...&Chen, Liaobin.(2021).Metal-drug nanoparticles-mediated osteolytic microenvironment regulation for enhanced radiotherapy of orthotopic osteosarcoma.CHEMICAL ENGINEERING JOURNAL,417,11.
MLA	Geng, Huan,et al."Metal-drug nanoparticles-mediated osteolytic microenvironment regulation for enhanced radiotherapy of orthotopic osteosarcoma".CHEMICAL ENGINEERING JOURNAL 417(2021):11.