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Author Spotlight: Transmitochondrial Cybrid Generation Using Cancer Cell Lines
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Author Spotlight: Transmitochondrial Cybrid Generation Using Cancer Cell Lines

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Mito-Specific Nutri-Hijacker Synergizing Mitochondrial Metabolism and Glycolysis Intervention for Enhanced Antitumor

Jingjing Yang1, Maoquan Chu2, Yuanlin Zhang3

  • 1School of Materials Science and Engineering, Institute of Nano and Biopolymeric Materials, Tongji University, Shanghai 201804, China.

ACS Applied Materials & Interfaces
|May 29, 2024
PubMed

Insights

This study introduces novel nanoparticles that target tumor mitochondria, suppressing glycolysis and generating reactive oxygen species (ROS) to eliminate cancer cells. This approach effectively halts tumor growth and prevents recurrence by disrupting metabolic rewiring.

Area of Science:

  • Biochemistry
  • Oncology
  • Nanotechnology

Background:

  • Tumors adapt to harsh conditions through metabolic rewiring, a phenotype switch.
  • While glycolysis deprivation was thought to be a tumor vulnerability, tumors can reprogram mitochondrial metabolism.
  • This mitochondrial reprogramming can lead to more aggressive cancer clones.

Purpose of the Study:

  • To develop a strategy to overcome tumor mitochondrial reprogramming.
  • To create an antiglycolytic nanoparticle (GRPP NP) that targets mitochondria.
  • To eliminate tumorigenic energy sources by disrupting both glycolysis and mitochondrial metabolism.

Main Methods:

  • Preparation of GRPP NPs containing a novel mitochondrial-targeted reactive oxygen species (ROS) generator (diIR780).
  • Utilizing GRPP NPs@diIR780 to catalyze endogenous glucose, suppressing glycolysis.
  • Releasing diIR780 to accumulate around mitochondria and generate toxic ROS.

Main Results:

  • GRPP NPs@diIR780 significantly suppressed tumor glycolysis.
  • Toxic ROS generation by diIR780 hampered crucial mitochondrial metabolism pathways.
  • The combined strategy effectively devastated tumor metabolic rewiring.

Conclusions:

  • This synchronous intervention strategy offers a promising approach to eradicate tumor lesions.
  • The developed nanoparticles can eliminate tumorigenic energy sources.
  • The treatment strategy shows potential for preventing tumor recurrence.
Keywords:
antitumor bioenergetic therapyglycolysis deprivationmetabolism programming breakingmitochondrial-targeting therapyoxidative phosphorylation

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