Advanced Cancer Starvation Therapy by Simultaneous Deprivation of Lactate and Glucose Using a MOF Nanoplatform. Issue 19 (7th August 2021)

• Record Type: Journal Article
• Authors: Yu, Jiantao; Wei, Zixiang; Li, Qing; Wan, Feiyan; Chao, Zhicong; Zhang, Xindan; Lin, Li; Meng, Hong; Tian, Leilei
• Is Part Of: Advanced science. Volume 8:Issue 19(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-08-07
• Subjects: glucose -- lactate -- metal‐organic frameworks -- monocarboxylate transporter 1 -- starvation therapy; Science -- Periodicals; 505
• DOI: 10.1002/advs.202101467
• Languages: English
• ISSNs: 2198-3844

Abstract

Abstract: 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 α ‐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 H2 O2 . 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. Abstract : Metal‐organic‐framework nanomedicines encapsulating an inhibitor of monocarboxylate transporters 1 and glucose oxidase are developed for efficient glucose depletion while inhibiting the lactate influx. At meanwhile, inhibiting the lactate influx can improve the intracellular oxygen pressure, which subsequently promotes the catalytic activity of glucose oxidase. Cancer cells are substantially killed from ATP shortage and high ROS levels.