Polythionoester Vesicle: An Efficient Polymeric Platform for Tuning HS Release.

Hydrogen sulfide (HS) serves as a key gaseous regulator that not only directs many physiological activities, but also manifests therapeutic benefits to many diseases. Developing HS vehicle platforms for its local delivery and long-acting release is important to achieve target gas therapy. Most of the known HS-donating polymers contain labile thioester scaffolds within their structures that suffer from the issue of low gas releasing efficiency. Here we present the use of thionoester, a constitutional isomer of thioester, as the functional unit to build a structural platform of cysteine-triggered HS donor polymer, polythionoester. Simple exchange of the sulfur and oxygen positions in the carbonyl sulfide scaffold makes the polythionoesters undergo a distinct mechanism of HS production, which can largely improve the gas-releasing efficiency (>80%). Moreover, the thionoester-containing block copolymers can self-assemble into vesicles in an aqueous media. We discover that control over the size effect can adjust the vesicle disassembly rate and gas-releasing kinetics. A tunable half-life of HS generation (2.6-9.8 h) can be accessed by tailoring the vesicle dimension. This allows such polymersomes to be potential as a gas nanodelivery system for long-lasting gas therapeutics.