Engineered nanoplatform mediated gas therapy enhanced ferroptosis for tumor therapy <i>in vivo</i>.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 39559423.
- Also identified by DOI 10.1016/j.bioactmat.2024.10.024 and PMC identifier 11570688.
- Licence recorded as CC BY-NC-ND.
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Abstract
The high glutathione (GSH) environment poses a significant challenge for inducing ferroptosis in tumor cells, necessitating the development of nanoplatforms that can deplete intracellular GSH. In this study, we developed an engineered nanoplatform (MIL-100@Era/L-Arg-HA) that enhances ferroptosis through gas therapy. First, we confirmed that the Fe element in the nanoplatform undergoes valence changes under the influence of high GSH and H<sub>2</sub>O<sub>2</sub> in tumor cells. Meanwhile, L-Arg generates NO gas in the presence of intracellular H<sub>2</sub>O<sub>2</sub>, which reacts with GSH. Additionally, Erastin depletes GSH by inhibiting the cystine/glutamate antiporter system, reducing cystine uptake and impairing GPX4, while also increasing intracellular H<sub>2</sub>O<sub>2</sub> levels by activating NOX4 protein expression. Through these combined GSH-depletion mechanisms, we demonstrated that MIL-100@Era/L-Arg-HA effectively depletes GSH levels, disrupts GPX4 function, and increases intracellular lipid ROS levels <i>in vitro</i>. Furthermore, this nanoplatform significantly inhibited tumor cell growth and extended the survival time of tumor-bearing mice <i>in vivo</i>. This engineered nanoplatform, which enhances ferroptosis through gas therapy, shows significant promise for ferroptosis-based cancer therapy and offers potential strategies for clinical tumor treatment.