The nanoquadruplex (PdH0.2)4Se demonstrates significant potential as a hydrogen-based anticancer agent, effectively inducing ferroptosis in cancer cells through NIR-controlled hydrogen release and subsequent ROS generation. The nanoparticle exhibits excellent tumor-targeted accumulation, photothermal imaging capability, and in vivo tumor growth inhibition with favorable biocompatibility, suggesting it represents a promising strategy for hydrogen-mediated cancer therapy.
Plain-Language Summary
Researchers designed a tiny nanoparticle made of palladium and selenium that can store and release hydrogen gas when exposed to near-infrared light (a type of invisible light). In laboratory tests with cancer cells and in mice, this nanoparticle accumulated in tumors and released hydrogen, which triggered a type of cancer cell death called ferroptosis (a process where cells accumulate damaging molecules). The nanoparticle slowed cancer cell growth and reduced tumor size in mice without apparent toxic effects.
Abstract
Hydrogen therapy as an emerging strategy for anticancer medicine is attracting attention. However, the limitations of effective hydrogen storage and release have hindered its development and application for hydrogen therapy. Herein, a high hydrogen storage nanoquadruplex (PdH0.2)4Se based on a palladium-selenium core has been designed and shows enhanced intratumoral accumulation via an enhanced permeability and retention (EPR) effect. High-efficiency hydrogen can be released from (PdH0.2)4Se, activated by near infrared irradiation (NIR), and combines with available selenium (Se) to produce highly toxic hydrogen selenide (H2Se), which in turn unbalances the GSH/GSSG ratio and induces ROS overproduction. The effect demonstrates that (PdH0.2)4Se irradiated by NIR significantly inhibits cancer cell proliferation, migration, invasion and angiogenesis in vitro. Furthermore, irradiation of (PdH0.2)4Se by NIR can induce significant ferroptosis of cancer cells by triggering mitochondrial dysfunction, ROS generation and lipid peroxidation-mediated oxidative damage in vitro. Finally, NIR irradiated (PdH0.2)4Se also exhibits tumor-targeted photothermal imaging, and inhibition of tumor growth in vivo activating cancer ferroptosis. Importantly, (PdH0.2)4Se demonstrates excellent safety and biocompatibility in vitro and in vivo. Thus together, our findings support the rational design of an effective hydrogen storage (PdH0.2)4Se nanoquadruplex with NIR-controlled release causing an unbalance of cellular GSH/GSSG and inducing cancer ferroptosis could be a highly efficient strategy for hydrogen-mediated cancer therapy.
