Polymeric nanoformulations aimed at cancer metabolism reprogramming with high specificity to inhibit tumor growth

Metabolic disorders of cancer cells create opportunities for metabolic interventions aimed at selectively eliminating cancer cells. Nevertheless, achieving this goal is challenging due to cellular plasticity and metabolic heterogeneity of cancer cells. This study presents a dual-drug-loaded, macroph...

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Bibliographic Details
Published in:Biomaterials science 2024-09, Vol.12 (19), p.576-59
Main Authors: Xia, Yu, Zhang, Ming-kang, Ye, Jing-jie, Niu, Mei-ting, Wang, Zi-yang, Dai, Xin-yi, He, Zhi-ling, Feng, Jun
Format: Article
Language:English
Subjects:
Cancer
Glucose
Glycolysis
Heterogeneity
Hydrogen peroxide
Macrophages
Metabolic disorders
Metabolism
Oxidation
Plastic foam
Tumors
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Summary:Metabolic disorders of cancer cells create opportunities for metabolic interventions aimed at selectively eliminating cancer cells. Nevertheless, achieving this goal is challenging due to cellular plasticity and metabolic heterogeneity of cancer cells. This study presents a dual-drug-loaded, macrophage membrane-coated polymeric nanovesicle designed to reprogram cancer metabolism with high specificity through integrated extracellular and intracellular interventions. This nanoformulation can target cancer cells and largely reduce their glucose intake, while the fate of intracellular glucose internalized otherwise is redirected at the specially introduced oxidation reaction instead of inherent cancer glycolysis. Meanwhile, it inhibits cellular citrate intake, further reinforcing metabolic intervention. Furthermore, the nanoformulation causes not only H 2 O 2 production, but also NADPH down-regulation, intensifying redox damage to cancer cells. Consequently, this nanoformulation displays highly selective toxicity to cancer cells and minimal harm to normal cells mainly due to metabolic vulnerability of the former. Once administered into tumor-bearing mice, this nanoformulation is found to induce the transformation of pro-tumor tumor associated macrophages into the tumor-suppressive phenotype and completely inhibit tumor growth with favourable biosafety. This study designed a BAY-876 and GOD co-loaded, macrophage membrane-coated polymeric nanovesicle to reprogram cancer metabolism, which demonstrated cancer-specific toxicity mainly due to the high metabolic vulnerability of cancer cells.
ISSN:2047-4830
2047-4849
2047-4849
DOI:10.1039/d4bm00887a