Nanoquadruplex-driven hydrogen therapy: NIR-controlled release for targeted cancer ferroptosis

Area of Science:

• Nanomedicine
• Biotechnology
• Materials Science

Background:

• Hydrogen therapy shows promise for cancer treatment but faces challenges in hydrogen storage and release.
• Developing effective delivery systems is crucial for advancing hydrogen-based anticancer strategies.

Purpose of the Study:

• To design and evaluate a novel nanoquadruplex, (PdH0.2)4Se, for enhanced hydrogen storage and controlled release in cancer therapy.
• To investigate the efficacy of (PdH0.2)4Se in inducing cancer cell death, specifically ferroptosis, through near-infrared (NIR) irradiation.

Main Methods:

• Synthesis of a palladium-selenium nanoquadruplex ((PdH0.2)4Se) with high hydrogen storage capacity.
• Evaluation of intratumoral accumulation using the enhanced permeability and retention (EPR) effect.
• NIR-triggered release of hydrogen and generation of hydrogen selenide (H2Se) to induce oxidative stress.
• In vitro and in vivo studies to assess cancer cell proliferation, migration, invasion, angiogenesis, and tumor growth inhibition.
• Analysis of ferroptosis induction mechanisms, including mitochondrial dysfunction and lipid peroxidation.
• In vitro and in vivo safety and biocompatibility assessments.

Main Results:

• The (PdH0.2)4Se nanoquadruplex demonstrated enhanced intratumoral accumulation via the EPR effect.
• NIR irradiation effectively released hydrogen, generating H2Se, which disrupted the GSH/GSSG ratio and induced reactive oxygen species (ROS) overproduction.
• In vitro studies showed significant inhibition of cancer cell proliferation, migration, invasion, and angiogenesis.
• NIR-irradiated (PdH0.2)4Se induced significant ferroptosis in cancer cells by triggering mitochondrial dysfunction, ROS generation, and lipid peroxidation.
• In vivo studies confirmed tumor-targeted photothermal imaging, inhibition of tumor growth, and activation of cancer ferroptosis.
• (PdH0.2)4Se exhibited excellent safety and biocompatibility.

Conclusions:

• The developed (PdH0.2)4Se nanoquadruplex is an effective platform for hydrogen storage and NIR-controlled hydrogen release.
• NIR-activated (PdH0.2)4Se induces cancer cell death via ferroptosis by unbalancing the cellular GSH/GSSG ratio and promoting ROS generation.
• This strategy offers a promising approach for hydrogen-mediated cancer therapy with demonstrated efficacy and safety in vitro and in vivo.