Gas‐Releasing Polymer Tubesomes: Boosting Gas Delivery of Nanovehicles via Membrane Stretching

Hydrogen sulfide (H₂S), one of the three gas signaling molecules, not only plays a vital role in mediating a series of cellular activities but also manifests exciting applications in clinical therapy. However, one main obstacle in using H₂S as a gaseous therapeutic agent is to realize on-demand storage and delivery of gas, and thus, it is of great importance to develop H₂S-donating vehicle platforms. Although a variety of polymer-based gas-releasing carriers have been designed, almost all the systems are limited to spherical structures. Here we explore the role of polymer self-assembled morphologies, especially toward those non-spherical nanostructures, on the H₂S release capacity. A kind of tubular polymersomes (i.e. tubesomes), formed by the membrane stretching of polythionoester-containing block copolymer vesicles, exhibit enhanced cysteine-responsive H₂S-releasing behavior in contrast to their spherical counterparts. Moreover, we found that the amount and rate of H₂S release from diverse polymersomes is relied on the extent of membrane elongation, which allows us to regulate the gas releasing kinetics through tailoring the membrane geometries. More importantly, it is demonstrated that the tubesomes as polymer-type H₂S donors have better anticancer performance than those spherical polymersomes. This would inspire new possibilities to boost gas therapeutic efficacy through shaping the morphology of gas nanovehicles.