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

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 -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 H 2 O 2 . 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.

Starvation, Ferroptosis, and Prodrug Therapy Synergistically Enabled by a Cytochrome c Oxidase like Nanozyme

“…strategy that works by depriving tumor cells of their energy supply. [17][18][19][20] Ferroptosis, the iron-dependent programmed cell death characterized by the accumulation of lipid peroxides, is also gaining increasing attention for cancer therapy. [21][22][23] To tackle the problem of serious off-target side-effects of conventional chemotherapy, prodrug therapy has been developed.…”

Nanoscale Zeolitic Imidazolate Framework (ZIF)–8 in Cancer Theranostics: Current Challenges and Prospects

“…H 2 O 2 produced by GOx generates hydroxyl radicals in the presence of HRP, thus killing tumor cells ( Figure 3 A). Yu et al fabricated the α–cyano–4–hydroxycinnamate (CHC)/GOx@ZIF–8 nanocomposite with GOx and MCT1 inhibitor CHC [ 48 ]. CHC inhibited lactate inward flow, which not only blocked one of the energy supply sources for cancer cells, but also reduced lactate metabolism to alleviate hypoxia at the tumor sites ( Figure 3 B).…”

A Comprehensive Review on the Use of Metal–Organic Frameworks (MOFs) Coupled with Enzymes as Biosensors

“…Cholesterol is another lipid-based biomolecule of relevance to biomedicine, as several cardiovascular diseases are related to its consumption and accumulation in the body. Thus, mapping cholesterol can be done by immobilizing a cholesterol oxidase (CHOD) (EC 1.1.3.6) onto metal-organic frameworks, which can allow for an accurate detection and concentration measurement in blood vessels or in other tissues in the body [120].…”