Material-driven nanoplatforms for precision hydrogen sulfide delivery

Long regarded as a toxic substance, hydrogen sulfide (H₂S) is now recognized as an essential gaseous signaling molecule that demonstrates dual modulation capacities in biological regulation and disease progression. Contemporary research delineates the dynamic enzymatic production pathways (mediated by cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3-MST)) alongside spatially organized signaling networks that govern its systemic influence on neuronal integrity, cardiovascular adaptation, and energy metabolism. Within the 10-100 μM range, this gaseous mediator exerts tissue-protective functions through vascular relaxation, suppression of inflammation, and inhibition of cell death. Conversely, imbalanced H₂S levels-whether insufficient or excessive-correlate with pathological cascades involving neoplastic transformation, synaptic degeneration, and redox imbalance. This analysis systematically examines progress in precision-controlled H₂S modulation technologies, particularly stimuli-responsive delivery architectures designed to resolve its concentration-dependent paradoxes. Emerging nanoscale delivery systems demonstrate enhanced spatiotemporal resolution in capitalizing on H₂S's dichotomous bioactivities for managing cerebrovascular pathologies, malignant proliferation, and mitochondrial dysfunction. Current challenges and opportunities are further discussed regarding therapeutic window optimization and biosafety profiling, proposing convergent approaches that integrate material science with systems biology to actualize H₂S's clinical potential.