Biodegradable copper-iodide clusters modulate mitochondrial function and suppress tumor growth under ultralow-dose...

Area of Science:

• Nanomedicine
• Biomedical Engineering
• Radiochemistry

Background:

• Copper (Cu) and iodine (I) are essential elements with potential anti-tumor properties.
• Challenges exist in delivering Cu and I ions effectively into tumor cells due to their high water solubility and potential for off-target release.
• Existing methods struggle with the stability of copper and iodide ions for therapeutic applications.

Purpose of the Study:

• To develop stable, mitochondria-targeted copper-iodine (Cu-I) cluster nanoparticles for tumor inhibition.
• To investigate the therapeutic efficacy of these nanoparticles in vitro and in vivo.
• To elucidate the mechanisms underlying tumor inhibition induced by these nanoparticles.

Main Methods:

• Synthesis of stable bovine serum albumin (BSA) radiation-induced phosphors (Cu-I@BSA) encapsulating Cu-I clusters.
• Conjugation of Cu-I@BSA with photosensitizers and targeting molecules.
• In vitro and in vivo studies evaluating tumor inhibition under low-dose X-ray irradiation.

Main Results:

• Cu-I@BSA nanoparticles exhibit bright radioluminescence and enhanced stability of Cu and I ions.
• Radioluminescence under X-ray irradiation activates conjugated photosensitizers to generate singlet oxygen, enhancing tumor inhibition.
• The heavy atom effect of iodine contributes to radiosensitization, leading to efficient tumor suppression in mice.

Conclusions:

• Mitochondria-targeted Cu-I@BSA nanoparticles provide a stable and effective platform for cancer therapy.
• The combined effects of singlet oxygen generation and iodine-induced radiosensitization lead to significant tumor inhibition.
• BSA-protected Cu-I clusters induce cancer cell death through multiple pathways, including mitochondrial dysfunction and DNA damage.