Rational design of non-toxic GOx-based biocatalytic nanoreactor for multimodal synergistic therapy and tumor metastasis suppression

doi:10.7150/thno.65399

	Rational design of non-toxic GOx-based biocatalytic nanoreactor for multimodal synergistic therapy and tumor metastasis suppression
	Hang, Lifeng 2; Zhang, Tao 3; Wen, Hua 2; Li, Meng 2; Liang, Lianbao 2; Tang, Xinfeng 4; Zhou, Chunze 1; Tian, JunZhang 2; Ma, Xiaofen 2; Jiang, Guihua 2
刊名	THERANOSTICS
	2021
卷号	11
关键词	Glucose oxidase tirapazamine metal-organic framework biocatalytic nanoreactor starvation therapy
ISSN号	1838-7640
DOI	10.7150/thno.65399
通讯作者	Jiang, Guihua(jianggh@gd2h.org.cn)
英文摘要	Rationale: Glucose oxidase (GOx)-based biocatalytic nanoreactors can cut off the energy supply of tumors for starvation therapy and deoxygenation-activated chemotherapy. However, these nanoreactors, including mesoporous silica, calcium phosphate, metal-organic framework, or polymer nanocarriers, cannot completely block the reaction of GOx with glucose in the blood, inducing systemic toxicity from hydrogen peroxide (H2O2) and anoxia. The low enzyme loading capacity can reduce systemic toxicity but limits its therapeutic effect. Here, we describe a real 'ON/OFF' intelligent nanoreactor with a core-shell structure (GOx + tirazapamine (TPZ))/ZIF-8@ZIF-8 modified with the red cell membrane (GTZ@Z-RBM) for cargo delivery. Methods: GTZ@Z-RBM nanoparticles (NPs) were prepared by the co-precipitation and epitaxial growth process under mild conditions. The core-shell structure loaded with GOx and TPZ was characterized for hydrate particle size and surface charge. The GTZ@Z-RBM NPs morphology, drug, and GOx loading/releasing abilities, system toxicity, multimodal synergistic therapy, and tumor metastasis suppression were investigated. The in vitro and in vivo outcomes of GTZ@Z-RBM NPs were assessed in 4T1 breast cancer cells. Results: GTZ@Z-RBM NPs could spatially isolate the enzyme from glucose in a physiological environment, reducing systemic toxicity. The fabricated nanoreactor with high enzyme loading capacity and good biocompatibility could deliver GOx and TPZ to the tumors, thereby exhausting glucose, generating H2O2, and aggravating hypoxic microenvironment for starvation therapy, DNA damage, and deoxygenation-activated chemotherapy. Significantly, the synergistic therapy effectively suppressed the breast cancer metastasis in mice and prolonged life without systemic toxicity. The in vitro and in vivo results provided evidence that our biomimetic nanoreactor had a powerful synergistic cascade effect in treating breast cancer. Conclusion: GTZ@Z-RBM NPs can be used as an 'ON/OFF' intelligent nanoreactor to deliver GOx and TPZ for multimodal synergistic therapy and tumor metastasis suppression.
资助项目	National Natural Science Foundation of China (NSFC)[51903162] ; National Natural Science Foundation of China (NSFC)[U1903120] ; National Natural Science Foundation of China (NSFC)[52001306] ; Science Foundation of Guangdong Second Provincial General hospital[YN2018-001] ; Doctoral workstation foundation of Guangdong Second Provincial General hospital[2019BSG2024] ; Key Research and Development Program of Anhui Province[202004J07020015] ; Science and Technology Projects in Guangzhou[202102020646]
WOS关键词	METAL-ORGANIC-FRAMEWORKS ; ONE-POT SYNTHESIS ; GLUCOSE-OXIDASE ; CANCER STARVATION ; STRATEGY ; ENZYMES
WOS研究方向	Research & Experimental Medicine
语种	英语
出版者	IVYSPRING INT PUBL
WOS记录号	WOS:000719124500004
资助机构	National Natural Science Foundation of China (NSFC) ; Science Foundation of Guangdong Second Provincial General hospital ; Doctoral workstation foundation of Guangdong Second Provincial General hospital ; Key Research and Development Program of Anhui Province ; Science and Technology Projects in Guangzhou
内容类型	期刊论文
源URL	[http://ir.hfcas.ac.cn:8080/handle/334002/126660]
专题	中国科学院合肥物质科学研究院
通讯作者	Jiang, Guihua
作者单位	1.Univ Sci & Technol China, Affiliated Hosp USTC 1, Intervent Radiol Dept, Div Life Sci & Med, Hefei 230001, Peoples R China 2.Guangdong Second Prov Gen Hosp, Dept Med Imaging, Guangzhou 518037, Peoples R China 3.Chinese Acad Sci, Inst Solid State Phys, Key Lab Mat Phys, HFIPS, Hefei 230031, Peoples R China 4.Univ Sci & Technol China, Sch Life Sci, Div Mol Med, Hefei Natl Lab Phys Sci Microscale, Hefei 230001, Peoples R China
推荐引用方式 GB/T 7714	Hang, Lifeng,Zhang, Tao,Wen, Hua,et al. Rational design of non-toxic GOx-based biocatalytic nanoreactor for multimodal synergistic therapy and tumor metastasis suppression[J]. THERANOSTICS,2021,11.
APA	Hang, Lifeng.,Zhang, Tao.,Wen, Hua.,Li, Meng.,Liang, Lianbao.,...&Jiang, Guihua.(2021).Rational design of non-toxic GOx-based biocatalytic nanoreactor for multimodal synergistic therapy and tumor metastasis suppression.THERANOSTICS,11.
MLA	Hang, Lifeng,et al."Rational design of non-toxic GOx-based biocatalytic nanoreactor for multimodal synergistic therapy and tumor metastasis suppression".THERANOSTICS 11(2021).