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Overcoming multidrug-resistant lung cancer by mitochondrial-associated ATP inhibition using nanodrugs

Jun-Young Park1,2, Gyu-Ho Lee3, Kwai Han Yoo4

  • 1Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, 21999, South Korea.

Journal of Nanobiotechnology
|January 12, 2023
PubMed

Insights

Researchers developed specific-sized carbon nanotube-doxorubicin nanodrugs to overcome multidrug resistance in lung cancer. These nanodrugs target tumor cells, induce mitochondrial damage, and inhibit ATP production for effective treatment.

Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Oncology

Background:

  • Multidrug resistance (MDR) and incomplete tumor destruction lead to lung cancer recurrence and poor survival.
  • Existing therapies struggle to overcome MDR and treat deep-seated tumors effectively.

Purpose of the Study:

  • To develop novel nanodrugs for enhanced intracellular drug delivery and overcoming MDR in lung cancer.
  • To investigate the efficacy of carbon nanotube-conjugated doxorubicin (CNT-DOX) in drug-resistant lung cancer cells.

Main Methods:

  • Covalent bonding of specific-sized carbon nanotubes with doxorubicin (DOX) to create CNT-DOX nanodrugs.
  • Evaluating intracellular drug internalization and retention in H69AR lung cancer cells (a DOX-resistant line).
  • Assessing the impact of CNT-DOX on mitochondrial function, ATP production, and overall therapeutic effect.

Main Results:

  • Designed nano-anticancer drugs with specific sizes did not activate drug resistance mechanisms in H69AR cells.
  • CNT-DOX demonstrated sustained intracellular presence in resistant cells, causing mitochondrial damage.
  • Suppression of ATP production and effective therapeutic outcomes in drug-resistant tumors were observed.

Conclusions:

  • Specific-sized nanodrugs combined with DOX overcome multidrug-resistant tumors.
  • Selective accumulation in tumor cells and ATP inhibition via mitochondrial damage are key mechanisms.
  • This approach offers a promising strategy for treating resistant lung cancers.
Keywords:
Carbon nanotubeDoxorubicinEndosomal escapeMitochondrial damageMultidrug resistant cellSmall cell lung cancer

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