Advanced Cancer Starvation Therapy by Simultaneous Deprivation of Lactate and Glucose Using a MOF Nanoplatform

Yu, Jiantao1,2; Wei, Zixiang2; Li, Qing2; Wan, Feiyan2; Chao, Zhicong2; Zhang, Xindan2; Lin, Li2; Meng, Hong1; Tian, Leilei2

2021-08-01

10.1002/advs.202101467

ADVANCED SCIENCE   影响因子和分区

2198-3844

Recent investigations reveal that lactate is not a waste product but a major energy source for cells, especially in the mitochondria, which can support cellular survival under glucose shortage. Accordingly, the new understanding of lactate prompts to target it together with glucose to pursue a more efficient cancer starvation therapy. Herein, zeolitic imidazolate framework-8 (ZIF-8) nanoplatforms are used to co-deliver alpha-cyano-4-hydroxycinnamate (CHC) and glucose oxidase (GOx) and fulfill the task of simultaneous depriving of lactate and glucose, resulting in a new nanomedicine CHC/GOx@ZIF-8. The synthesis conditions are carefully optimized in order to yield monodisperse and uniform nanomedicines, which will ensure reliable and steady therapeutic properties. Compared with the strategies aiming at a single carbon source, improved starvation therapy efficacy is observed. Besides, more than boosting the energy shortage, CHC/GOx@ZIF-8 can block the lactate-fueled respiration and relieve solid tumor hypoxia, which will enhance GOx catalysis activity, depleting extra glucose, and producing more cytotoxic H2O2. By the synergistically enhanced anti-tumor effect, both in vitro and in vivo cancer-killing efficacies of CHC/GOx@ZIF-8 show twice enhancements than the GOx mediated therapy. The results demonstrate that the dual-depriving of lactate and glucose is a more advanced strategy for strengthening cancer starvation therapy.

glucose lactate metal-organic frameworks monocarboxylate transporter 1 starvation therapy

SCI ; EI

英语

ESI高被引

通讯

National Natural Science Foundation of China[51973089] ; Shenzhen Science and Technology Innovation Commission[KQTD20170810111314625] ; Shenzhen Fundamental Research Programs["JCYJ20180302153406868","JCYJ20170817105645935"]

Chemistry ; Science & Technology - Other Topics ; Materials Science

Chemistry, Multidisciplinary ; Nanoscience & Nanotechnology ; Materials Science, Multidisciplinary

WOS:000682506800001

WILEY

20213210750757

Diseases ; Glucose ; Glucose sensors ; Hydrogen peroxide ; Lactic acid ; Medical nanotechnology ; Tumors

Biological Materials and Tissue Engineering:461.2 ; Biology:461.9 ; Biomedical Equipment, General:462.1 ; Nanotechnology:761 ; Organic Compounds:804.1 ; Inorganic Compounds:804.2

Web of Science

1.Peking Univ, Sch Adv Mat, Shenzhen Grad Sch, Shenzhen 518055, Peoples R China
2.Southern Univ Sci & Technol, Dept Mat Sci & Engn, 1088 Xueyuan Blvd, Shenzhen 518055, Guangdong, Peoples R China

Yu, Jiantao,Wei, Zixiang,Li, Qing,et al. Advanced Cancer Starvation Therapy by Simultaneous Deprivation of Lactate and Glucose Using a MOF Nanoplatform[J]. ADVANCED SCIENCE,2021,8.

Yu, Jiantao.,Wei, Zixiang.,Li, Qing.,Wan, Feiyan.,Chao, Zhicong.,...&Tian, Leilei.(2021).Advanced Cancer Starvation Therapy by Simultaneous Deprivation of Lactate and Glucose Using a MOF Nanoplatform.ADVANCED SCIENCE,8.

Yu, Jiantao,et al."Advanced Cancer Starvation Therapy by Simultaneous Deprivation of Lactate and Glucose Using a MOF Nanoplatform".ADVANCED SCIENCE 8(2021).