A hypothermia-sensitive micelle with controlled release of hydrogen sulfide for protection against anoxia/reoxygenation-induced cardiomyocyte injury

Abstract

Hydrogen sulfide (H2S) provided a potential strategy to protect heart from ischemia-reperfusion injury (IRI). However, controllable and continuous H2S level for long periods of time remained challengeable in the aspect of maintaining viability of heart in cold storage. Hence, we investigated the protective efficiency of hypothermia-sensitive micelle with controlled release of H2S for cardiomyocyte through in vitro anoxia/reoxygenation (A/R) cardiomyocyte models. This micelle was fabricated through the self-assembly of an amphiphilic deblock copolymer methoxy poly(ethylene glycol)-poly(N-pyrrolidine-formyl-caprolactone-co-thiobenzamide-caprolactone) (mPEG-P(VPyCL-co-TBA-CL)). Benefiting from the reversible lower critical solution temperature (LCST)-type behavior with low cloud point (Tcp) of 13 °C, self-assembled micelle could control the release of H2S in response to temperature under the thiol-triggered condition. Noteworthily, with the disassembly of micelle at 4 °C, micelles enjoyed a controllable and continuous release profile of H2S. By mimicking the cold storage of the heart against IRI, released H2S from micelle was demonstrated to provide a significant protection for cardiomyocytes against A/R-induced injury. Taken together, we envisioned that this work offered a potential hypothermia-sensitive material with controlled release of H2S promising for heart preservation against IRI in cold storage.