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O2-Supplying Nanozymes Alleviate Hypoxia and Deplete Lactate to Eliminate Tumors and Activate Antitumor Immunity

文献类型：期刊论文

作者Sun, Luyao1; Gao, Wendong2; Liu, Jie1; Wang, Jingjing1; Li, Li1; Yu, Haijun3,4; Xu, Zhi Ping1
刊名ACS APPLIED MATERIALS & INTERFACES
出版日期2022-12-14
页码14
ISSN号1944-8244
关键词layered double hydroxides O2 self-generation hypoxia relief lactate depletion tumor microenvironment regulation tumor-associated macrophage reprogramming
DOI10.1021/acsami.2c18960
通讯作者Li, Li(l.li2@uq.edu.au) ; Xu, Zhi Ping(gordonxu@uq.edu.au)
英文摘要Direct hypoxia alleviation and lactate depletion in the tumor microenvironment (TME) are promising for effective cancer therapy but still very challenging. To address this challenge, the current research directly reshapes the TME for inhibiting tumor growth and activating the antitumor immunity using a drug-free nanozyme. Herein, the acid-sensitive nanozymes were constructed based on peroxidized layered double hydroxide nanoparticles for O2 self-supply and self-boosted lactate depletion. The coloading of partially cross-linked catalase and lactate oxidase enabled the acid-sensitive nanozymes to promote three reactions, that is, (1) H2O2 generation from MgO2 hydrolysis (30% at pH 7.4 vs 63% at pH 6.0 in 8 h); (2) O2 generation from H2O2 (12% at pH 7.4 vs 21% at pH 6.0 in 2 h); and (3) lactate depletion by in situ generated O2 (50% under hypoxia vs 75% under normoxia in 24 h in vitro) in parallel or tandem. These promoted reactions together efficiently induced colon cancer cell apoptosis under the hypoxic conditions, significantly inhibited tumor growth (>95%), and suppressed distant tumor growth upon seven administrations in every 3 days and moreover transformed the immunosuppressive tumor into "hot" one in the colon tumor-bearing mouse model. This is the first example for a nanozyme that supplies sufficient O2 for hypoxia relief and lactate depletion, thus providing a new insight into drug-free nanomaterial-mediated TME-targeted cancer therapy.
WOS关键词CELLS ; PEROXIDE
资助项目Australian Research Council (ARC)[DP190103486] ; UQ Research Training Scholarship
WOS研究方向Science & Technology - Other Topics ; Materials Science
语种英语
出版者AMER CHEMICAL SOC
WOS记录号WOS:000898900400001
源URL[http://119.78.100.183/handle/2S10ELR8/304171]  
专题新药研究国家重点实验室
通讯作者Li, Li; Xu, Zhi Ping
作者单位1.Univ Queensland, Australian Inst Bioengn & Nanotechnol, Brisbane, Qld 4072, Australia
2.Queensland Univ Technol, Ctr Biomed Technol, Brisbane, Qld 4059, Australia
3.Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
4.Chinese Acad Sci, Ctr Pharmaceut, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Sun, Luyao,Gao, Wendong,Liu, Jie,et al. O2-Supplying Nanozymes Alleviate Hypoxia and Deplete Lactate to Eliminate Tumors and Activate Antitumor Immunity[J]. ACS APPLIED MATERIALS & INTERFACES,2022:14.
APA Sun, Luyao.,Gao, Wendong.,Liu, Jie.,Wang, Jingjing.,Li, Li.,...&Xu, Zhi Ping.(2022).O2-Supplying Nanozymes Alleviate Hypoxia and Deplete Lactate to Eliminate Tumors and Activate Antitumor Immunity.ACS APPLIED MATERIALS & INTERFACES,14.
MLA Sun, Luyao,et al."O2-Supplying Nanozymes Alleviate Hypoxia and Deplete Lactate to Eliminate Tumors and Activate Antitumor Immunity".ACS APPLIED MATERIALS & INTERFACES (2022):14.

入库方式： OAI收割

来源：上海药物研究所

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