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Updated: Sep 15, 2025

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer
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Lung-targeted feedback regulation of the mitochondrial ATP synthesis pathway for orthotopic tumor suppression

Zhou Jiang1, Songlan Pan2, Jianhua Chen1

  • 1Department of Thoracic Medicine, Affiliated Cancer Hospital of Xiangya School of Medicine, Hunan Cancer Hospital, Central South University, Changsha 410006, China.

Journal of Materials Chemistry. B
|July 15, 2025
PubMed

Insights

This study introduces a novel nanomedicine strategy to target cancer by inhibiting mitochondrial ATP production. This feedback-controlled approach minimizes side effects by reducing drug release when ATP levels normalize.

Area of Science:

  • Biomedical Engineering
  • Nanomedicine
  • Cancer Therapeutics

Background:

  • Adenosine triphosphate (ATP) fuels cancer progression but targeting it is challenging due to its essential role in normal cells.
  • Existing ATP-targeting strategies lack selectivity, leading to significant side effects.
  • Feedback inhibition, a natural regulatory mechanism, offers a potential solution for targeted cancer treatment.

Purpose of the Study:

  • To develop a mitochondria-targeted nanomedicine system for cancer treatment using feedback inhibition of ATP synthesis.
  • To create an ATP-responsive metal-organic framework (ZIF-90) for controlled drug delivery.
  • To investigate the efficacy of this system in reducing tumor ATP levels with minimal off-target effects.

Main Methods:

  • Fabrication of an ATP-responsive ZIF-90/AIPH/BE nanocomplex for mitochondria-targeted delivery.
  • Utilizing the competitive binding between ATP and Zn2+ in ZIF-90 to trigger drug release.
  • Assessing the nanocomplex's pulmonary accumulation, mitochondria-targeting capability, and ATP depletion efficacy.
  • Implementing a negative feedback loop to regulate drug release based on ATP levels.

Main Results:

  • The ZIF-90/AIPH/BE nanocomplex demonstrated high pulmonary accumulation and effective mitochondria targeting.
  • ATP presence triggered nanoparticle disintegration and release of AIPH and bedaquiline (BE).
  • Released AIPH and BE significantly reduced ATP production, leading to mitochondrial ATP depletion.
  • A negative feedback mechanism was observed, restricting further drug release upon ATP reduction.

Conclusions:

  • A novel ATP-responsive nanomedicine system based on ZIF-90 was successfully developed for targeted cancer therapy.
  • The feedback inhibition mechanism effectively controls drug release, enhancing therapeutic specificity and minimizing side effects.
  • This approach offers a promising new avenue for developing advanced nanomedicines targeting metabolic pathways in diseases like cancer.

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