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Enzyme-Instructed Self-Assembly Reprograms Fatty Acid Metabolism for Cancer Therapeutics.

Hongjian He1,2, Haonan Lin1,2, Le Wang1,2

  • 1Department of Electrical and Computer Engineering, Boston University, Boston, MA, 02215, USA.

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|April 29, 2025
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Summary
This summary is machine-generated.

Enzyme-instructed self-assembly (EISA) therapy boosts cancer cell lipid metabolism and fatty acid uptake. Inhibiting fatty acid uptake enhances EISA

Keywords:
cancer treatmentlipid metabolismpeptideself‐assembly

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Area of Science:

  • Biomedical Engineering
  • Cancer Research
  • Molecular Imaging

Background:

  • Enzyme-instructed self-assembly (EISA) is a developing cancer treatment strategy.
  • The metabolic adaptations of cancer cells to EISA therapy are not well understood.

Purpose of the Study:

  • To investigate the metabolic effects of EISA on cancer cells.
  • To explore the role of fatty acid metabolism in cancer cell resistance to EISA.
  • To evaluate combination therapies involving EISA and fatty acid metabolism modulation.

Main Methods:

  • Stimulated Raman scattering (SRS) imaging was utilized to observe cellular changes.
  • Experiments were conducted in vitro and using 3D-culture spheroid models.
  • Fatty acid uptake inhibition and supplementation were employed to modulate cancer cell metabolism.

Main Results:

  • EISA treatment significantly increased lipid catabolism and fatty acid (FA) uptake in cancer cells.
  • Elevated FA uptake contributed to cancer cell resistance against EISA therapy.
  • Combined EISA treatment with FA uptake inhibition demonstrated enhanced cancer suppression.
  • FA supplementation rescued cancer cells from EISA-induced stress and growth inhibition.

Conclusions:

  • EISA profoundly impacts cancer cell metabolism, particularly lipid and FA pathways.
  • Targeting FA metabolism alongside EISA presents a promising strategy for improved cancer therapy.
  • Understanding metabolic reprogramming is crucial for optimizing EISA-based cancer treatments.