On-demand therapeutic delivery of hydrogen sulfide aided by biomolecules.

Hydrogen sulfide (HS), known as the third gasotransmitter, exerts various physiological functions including cardiac protection, angiogenesis, anti-inflammatory, and anti-cancer capability. Given its promising therapeutic potential as well as severe perniciousness if improper use, the sustained and tunable HS delivery systems are highly required for HS-based gas therapy with enhanced bioactivity and reduced side effects. To this end, a series of stimuli-responsive compounds capable of releasing HS (termed HS donors) have been designed over the past two decades to mimic the endogenous generation of HS and elucidate the biological functions. Further to improve the stability of HS donors and achieve the targeted delivery, various delivery systems have been constructed. In this review, we focus on the recent advances of an emerging subset, biomolecular-based HS delivery systems, which combine HS donors with biomolecular vectors including polysaccharide, peptide, and protein. We demonstrated their basic structures, building strategies, and therapeutic applications respectively to unfold their inherent merits endued by biomolecules including biocompatibility, biodegradability as well as expansibility. The varied development potentials of biomolecular-based HS delivery systems based on their specific properties are also discussed. At the end, brief future outlooks and upcoming challenges are presented as well.