Impairing Tumor Metabolic Plasticity via a Stable Metal‐Phenolic‐Based Polymeric Nanomedicine to Suppress Colorectal Cancer

Targeting metabolic vulnerability of tumor cells is a promising anticancer strategy. However, the therapeutic efficacy of existing metabolism‐regulating agents is often compromised due to tolerance resulting from tumor metabolic plasticity, as well as their poor bioavailability and tumor‐targetability. Inspired by the inhibitive effect of N‐ethylmaleimide on the mitochondrial function, a dendronized‐polymer‐functionalized metal‐phenolic nanomedicine (pOEG‐b‐D‐SH@NP) encapsulating maleimide‐modified doxorubicin (Mal‐DOX) is developed to enable improvement in the overall delivery efficiency and inhibition of the tumor metabolism via multiple pathways. It is observed that Mal‐DOX and its derived nanomedicine induces energy depletion of CT26 colorectal cancer cells more efficiently than doxorubicin, and shifts the balance of programmed cell death from apoptosis toward necroptosis. Notably, pOEG‐b‐D‐SH@NP simultaneously inhibits cellular oxidative phosphorylation and glycolysis, thus potently suppressing cancer growth and peritoneal intestinal metastasis in mouse models. Overall, the study provides a promising dendronized‐polymer‐derived nanoplatform for the treatment of cancers through impairing metabolic plasticity.

• Publication year

  2023

• Venue

  Advances in Materials

• Publication date

  2023-03-14

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.1002/adma.202300548PMID 36917817
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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