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Cellular defense system-destroying nanoparticles as a platform for enhanced chemotherapy against drug-resistant

Boyi Niu1, Kaixin Liao1, Yixian Zhou1

  • 1School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.

Materials Science & Engineering. C, Materials for Biological Applications
|December 3, 2021
PubMed

Insights

This study introduces novel nanoparticles that deplete glutathione (GSH), a cellular defense mechanism in cancer. This depletion enhances chemotherapy efficacy, showing promise for improved cancer treatment with reduced toxicity.

Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Cancer Therapy

Background:

  • Glutathione (GSH) is a cellular defense system that hinders cancer therapy outcomes through antioxidation and detoxification.
  • Depleting GSH can enhance therapies like reactive oxygen species (ROS)-based treatments and chemotherapy.
  • Current GSH depletion strategies often lack clear biosafety and involve complex multi-component delivery.

Purpose of the Study:

  • To develop a novel glutathione (GSH)-depleting carrier platform using disulfide-bridged mesoporous organosilica nanoparticles (MONs).
  • To investigate the potential of this platform to disrupt the cellular defense system for improved cancer therapy.
  • To evaluate the efficacy of cisplatin-loaded MONs (Pt@MONs) in treating drug-resistant non-small cell lung cancer.

Main Methods:

  • Fabrication of disulfide-bridged mesoporous organosilica nanoparticles (MONs).
  • Loading of chemotherapeutic drug cisplatin into MONs (Pt@MONs).
  • In vitro and in vivo evaluation of Pt@MONs for GSH depletion, drug delivery, and anti-cancer effects in non-small cell lung cancer models.

Main Results:

  • The developed MONs effectively depleted intracellular glutathione (GSH) in cancer cells.
  • Disulfide bond cleavage in MONs led to GSH consumption and nanoparticle degradation.
  • Pt@MONs demonstrated efficient GSH depletion, enhanced platinum-DNA adduct formation, and induced apoptosis, leading to significant tumor growth inhibition in vivo.
  • The treatment showed no marked toxicity in the evaluated models.

Conclusions:

  • Disulfide-bridged MONs serve as an effective GSH-depleting platform for cancer therapy.
  • This approach disrupts the cellular defense system, enhancing chemotherapeutic efficacy.
  • The developed nanoparticle platform offers a promising strategy for improved cancer treatment with good biosafety profiles.
Keywords:
ChemotherapyCisplatin resistanceDisulfide bondsGlutathione depletionMesoporous organosilica nanoparticles (MONs)

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