Polynorbornene-derived block copolymer micelles via ring-opening metathesis polymerization with capacity of hydrogen sulfide generation

Hydrogen sulfide (H₂S), a gasotransmitter, has recently attracted significant attention for its therapeutic properties. In order to achieve controlled H₂S release, polymer-based H₂S donors are essential. In this report, we constructed amphiphilic block copolymer (PNEG-b-PNSATO) consisting of norbornene-mPEG (Nor-mPEG) as a hydrophilic part and norbornene-conjugated SATO moiety (Nor-SATO) as a hydrophobic part via ring-opening metathesis polymerization (ROMP). Different SATO donor contents were tested with different hydrophilic/hydrophobic polymer ratios in order to find the ideal block copolymer to release H₂S, for example, PNEG_8k-b-PNSATO_4k, PNEG_8k-b-PNSATO_8k, PNEG_8k-b-PNSATO_12k. The block copolymers could form micelles with a range of sizes from 41 to 57 nm. The PNEG-b-PNSATO polymeric micelles release H₂S at a prolonged release rate (peak time of 60–70 min). PNEG-b-PNSATO polymeric micelles were assessed by MTT assay against L929 cells, showing excellent biocompatibility. Fluorescent imaging was used to gauge H₂S release. Additionally, the PNEG-b-PNSATO polymeric micelles were demonstrated to protect against oxidative damage induced by a lethal dose of H₂O₂, demonstrating the possibility of using this system to achieve H₂S therapeutic effects.