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

Hydrogen sulfide (HS) gas therapygarners significant attention for its potential to improve outcomes in various disease treatments. The quantitative control of HS release is crucial for effective the rapeutic interventions; however, traditional researchon HS 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 HS release model that leverages the dynamic hydrolysis of HS donorswithin the bloodstream. Calcium sulfide nanoparticles (CaS NPs) withmicrosolubility characteristics exhibit continuous HS release, surpassing 24 h at normal blood flow velocities. The extended-release profile demonstrates superior potential in aligning with the bell-shapedpharmacological effect of HS, compared to NaHS. Moreover, we synthesisedrare earth-doped CaS NPs (CaS: Eu, Sm NPs) tha texhibit persistent luminescence, enabling visualisation of the continuous HS release in trials. Our results demonstrate that lowdose CaS: Eu, Sm 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 HS levels in treating epilepsy and tumors. This innovative slow-release, in-situ HS the rapeutic approach via hydrolysis rejuvenates the development of HS-basedtherapeutics.