Manganese-deposited iron oxide promotes tumor-responsive ferroptosis that synergizes the apoptosis of cisplatin

doi:10.7150/thno.53346

	Manganese-deposited iron oxide promotes tumor-responsive ferroptosis that synergizes the apoptosis of cisplatin
	Cheng, Junjie 2; Zhu, Yang 2; Xing, Xin 3; Xiao, Jianmin 4; Chen, Hui 5; Zhang, Hongwei 2; Wang, Dan 5; Zhang, Yuanyuan 6; Zhang, Guilong 1; Wu, Zhengyan 4
刊名	THERANOSTICS
	2021
卷号	11
关键词	cisplatin ferroptosis anticancer theranostics manganese
ISSN号	1838-7640
DOI	10.7150/thno.53346
通讯作者	Zhang, Guilong(glzhang@bzmc.edu.cn) ; Wu, Zhengyan(zywu@ipp.ac.cm) ; Liu, Yangzhong(liuyz@ustc.edu.cn)
英文摘要	Background: Ferroptosis is a form of iron-dependent programmed cell death that differs from apoptosis with regards to both mechanism and cell morphology. Therefore, ferroptotic-based cancer therapy has shown significant potential to overcome the weaknesses of conventional therapeutics mediated by apoptosis pathways. Effective ferroptosis can be induced by the intracellular Fenton reaction that is dependent on the adequate supply of iron ions and H2O2 in cells. However, these are often insufficient due to intrinsic cellular regulation. Methods: In this study, we designed a cisplatin prodrug-loaded manganese-deposited iron oxide nanoplatform (Pt-FMO) to trigger intracellular cascade reactions that lead to generation of reactive oxygen species (ROS) to enhance ferroptotic effect. The Pt-FMO causes the tumor microenvironment responsive to release manganese, iron ions and Pt-drugs. As manganese is an element that is able to catalyze the Fenton reaction more effectively than iron, coupled with the Pt-drugs that can promote generation of H2O2 in cells, the Pt-FMO is expected to significantly strengthen catalysis of the Fenton reaction, which favors the ferroptotic effect. Moreover, the Pt-drugs will eventually function as cisplatin. Thus, Pt-FMO is an ideal candidate for tumor ferroptotic combined with apoptotic treatment. Results: In vivo results demonstrated that, at a dosage of only 8.89% Pt content, Pt-FMO is able to achieve a similar treatment effect as cisplatin. Hence, Pt-FMO exhibited significantly lower systemic toxicity compared to cisplatin. Additionally, Pt-FMO exhibits effective T-2-weighted MRI enhancement for tumor imaging. Conclusion: The Pt-FMO nanoplatform is designed to introduce mutual beneficial cascade reactions for promoting ferroptosis and apoptosis in combination with tumor MRI. The Pt-FMO system, which causes ferroptosis combined with apoptosis, can efficiently induce tumor cell death.
资助项目	National Key R&D Program of China[2020YFA0710700] ; National Key R&D Program of China[2017YFA0505400] ; National Natural Science Foundation of China[21877103] ; National Natural Science Foundation of China[52021002] ; Anhui Provincial Natural Science Foundation[1908085QB77] ; Special Project of Central Government for Local Science and Technology Development of Shandong Province[YDZX20203700001291] ; Users with Excellence Program of Hefei Science Center CAS[2020HSC-UE016]
WOS研究方向	Research & Experimental Medicine
语种	英语
出版者	IVYSPRING INT PUBL
WOS记录号	WOS:000629071700021
资助机构	National Key R&D Program of China ; National Natural Science Foundation of China ; Anhui Provincial Natural Science Foundation ; Special Project of Central Government for Local Science and Technology Development of Shandong Province ; Users with Excellence Program of Hefei Science Center CAS
内容类型	期刊论文
源URL	[http://ir.hfcas.ac.cn:8080/handle/334002/121322]
专题	中国科学院合肥物质科学研究院
通讯作者	Zhang, Guilong; Wu, Zhengyan; Liu, Yangzhong
作者单位	1.Binzhou Med Univ, State Adm Tradit Chinese Med China, Sch Pharm, Key Lab Prescript Effect & Clin Evaluat, Yantai 264003, Peoples R China 2.Univ Sci & Technol China, Dept Pharm, Affiliated Hosp USTC 1, Div Life Sci & Med,Dept Chem, Hefei 230001, Peoples R China 3.Wannan Med Coll, Dept Stomatol, Affiliated Hosp 1, Wuhu 241000, Peoples R China 4.Chinese Acad Sci, Hefei Inst Phys Sci, Key Lab High Magnet Field & Ion Beam Phys Biol, Hefei 230031, Peoples R China 5.Anhui Med Univ, Stomatol Hosp & Coll, Dent Implant Ctr, Key Lab Oral Dis Res Anhui Prov, Hefei 230032, Peoples R China 6.Anhui Med Univ, Sch Life Sci, Hefei 230032, Peoples R China
推荐引用方式 GB/T 7714	Cheng, Junjie,Zhu, Yang,Xing, Xin,et al. Manganese-deposited iron oxide promotes tumor-responsive ferroptosis that synergizes the apoptosis of cisplatin[J]. THERANOSTICS,2021,11.
APA	Cheng, Junjie.,Zhu, Yang.,Xing, Xin.,Xiao, Jianmin.,Chen, Hui.,...&Liu, Yangzhong.(2021).Manganese-deposited iron oxide promotes tumor-responsive ferroptosis that synergizes the apoptosis of cisplatin.THERANOSTICS,11.
MLA	Cheng, Junjie,et al."Manganese-deposited iron oxide promotes tumor-responsive ferroptosis that synergizes the apoptosis of cisplatin".THERANOSTICS 11(2021).