In Situ Slow-Release Hydrogen Sulfide Therapeutics for Advanced Disease Treatments

Hydrogen sulfide (H₂S) gas therapygarners significant attention for its potential to improve outcomes in various disease treatments. The quantitative control of H₂S release is crucial for effective the rapeutic interventions; however, traditional researchon H₂S therapy frequently utilizes static release models and neglects the dynamic nature of blood flow. In this study, we propose a novel slow-release in-situ H₂S release model that leverages the dynamic hydrolysis of H₂S donorswithin the bloodstream. Calcium sulfide nanoparticles (CaS NPs) withmicrosolubility characteristics exhibit continuous H₂S release, surpassing 24 h at normal blood flow velocities. The extended-release profile demonstrates superior potential in aligning with the bell-shapedpharmacological effect of H₂S, compared to NaHS. Moreover, we synthesisedrare earth-doped CaS NPs (CaS: Eu²⁺, Sm³⁺ NPs) tha texhibit persistent luminescence, enabling visualisation of the continuous H₂S release in trials. Our results demonstrate that lowdose CaS: Eu²⁺, Sm³⁺ NPs significantly reduces seizureduration to 1.2 ± 0.7 minutes, while high dose effectively suppresses colontumor growth with a tumor inhibition rate of 54%. Remarkably, these findings closely resemble endogenous H₂S levels in treating epilepsy and tumors. This innovative slow-release, in-situ H₂S the rapeutic approach via hydrolysis rejuvenates the development of H₂S-basedtherapeutics.