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Tumor Microenvironment-Responsive Cu/CaCO3 -Based Nanoregulator for Mitochondrial Homeostasis Disruption-Enhanced

Yajie Zhao1,2, Yulong Bian1,2, Xiao Xiao1,2

  • 1State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, P. R. China.

Small (Weinheim an Der Bergstrasse, Germany)
|August 23, 2022
PubMed

Insights

Intelligent nanoparticles deliver oxygen and ions to tumor sites, enhancing cancer therapy by generating reactive oxygen species (ROS) through chemodynamic and sonodynamic approaches.

Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Cancer Therapy

Background:

  • Tumor microenvironment (TME) characteristics like high glutathione (GSH) and hypoxia limit reactive oxygen species (ROS) cancer therapy.
  • Existing therapies struggle with insufficient hydrogen peroxide (H2O2) levels in the TME.

Purpose of the Study:

  • To develop TME-responsive nanoparticles for enhanced ROS-mediated cancer therapy.
  • To overcome limitations of GSH, hypoxia, and low H2O2 in the TME.

Main Methods:

  • Fabrication of intelligent copper-dropped calcium carbonate loading sonosensitizer Ce6 nanoparticles (Cu/CaCO3@Ce6, CCC NPs).
  • Utilizing CCC NPs for TME-responsive self-supply of oxygen.
  • Employing Ca2+ and Cu2+ release for enhanced chemodynamic therapy (CDT) and sonodynamic therapy (SDT).

Main Results:

  • CCC NPs release Ca2+, Cu2+, and Ce6 in the TME, consuming GSH and generating hydroxyl radicals via Fenton-like reactions.
  • Ultrasound irradiation amplifies oxidative stress through singlet oxygen release (SDT).
  • Ca2+ influx disrupts mitochondria, further increasing oxidative stress.

Conclusions:

  • The developed CCC NPs effectively address TME limitations for ROS-cancer therapy.
  • Ca2+-overloading-strengthened CDT/SDT offers a promising strategy for cancer treatment.
  • Cu-dropped CaCO3-based nanoregulators represent a new paradigm in ROS-contributed cancer therapy.
Keywords:
CaCO 3 biomineralscalcium overloadmitochondrial disruptionsynergistic therapytumor microenvironment-responsive (TME-responsive)

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