A glutathione-responsive polyphenol - Constructed nanodevice for double roles in apoptosis and ferroptosis

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Therapy

Background:

• Cancer treatment often relies on chemotherapy, but drug resistance limits efficacy.
• Apoptosis is a key cell death pathway, yet cancer cells can resist it.
• Ferroptosis, a distinct cell death pathway involving reactive oxygen species (ROS), offers an alternative therapeutic strategy.

Purpose of the Study:

• To design a novel drug delivery system that combines ferroptosis and apoptosis induction for enhanced cancer cell killing.
• To leverage Doxorubicin (DOX)-induced reactive oxygen species (ROS) to bridge these two cell death pathways.
• To develop a stable and effective nanocarrier for targeted cancer therapy.

Main Methods:

• A facile self-assembly method was used to prepare Doxorubicin (DOX)-loaded nanocomplexes.
• The nanocomplexes were composed of DOX, Pluronic F-68, tannic acid (TA), and iron ions (Fe3+).
• In vitro and in vivo experiments were conducted to evaluate the efficacy and targeting ability of the nanocomplexes.

Main Results:

• DOX@F-68/TA/Fe3+ nanocomplexes demonstrated enhanced intracellular oxidative stress, leading to both apoptosis and ferroptosis in tumor cells.
• Tannic acid and iron ions improved nanocarrier stability and facilitated the ferroptotic effect.
• In vivo studies showed efficient tumor targeting and significant inhibition of tumor development after intravenous injection.

Conclusions:

• The developed DOX@F-68/TA/Fe3+ nanocomplexes represent a promising strategy for overcoming drug resistance by inducing dual cell death pathways (apoptosis and ferroptosis).
• This combination therapy approach, driven by DOX-induced ROS, offers a potent method for cancer treatment.
• The nanocarrier system exhibits excellent tumor targeting and therapeutic efficacy in vivo.