Synthesis and cellular affinity of a water-soluble sulfated diselenide compound as a H₂O₂-responsive ionic cross-linker

Because various stimuli can affect living organisms, substances that response to stimuli, such as H₂O₂, have been studied for biomaterials. To synthesize a biocompatible H₂O₂-responsive ionic cross-linker, we synthesized a water-soluble H₂O₂-responsive diselenide compounds containing both sulfate end groups (diSe-SO₄). The synthesis of diSe-SO₄ was evaluated by ¹H NMR and FT-IR. H₂O₂ responsiveness was evaluated by UV–vis spectra, FT-IR, and XPS. The optical density at 303 nm due to diselenide in diSe-SO₄ was decreased in the H₂O₂ concentration increased. FT-IR and XPS results showed new peaks at 880 cm and 3500 cm⁻¹, and at 63.0 eV, respectively, due to oxidized Se, which indicated the cleavage of the diselenide bond in diSe-SO₄ as the H₂O₂ concentration increased. The ionic binding efficiency of diSe-SO₄ to cationic materials was confirmed by measuring the zeta-potential difference (from –15.6 mV to 10.3 mV) before and after mixing with chitosan. MRC-5 cell viability and apoptosis in the presence of diSe-SO₄ was evaluated using a CCK-8 assay and FACS, respectively. A high cell viability exceeding 95% was observed at 500 μM diSe-SO₄ over 48 h of culture. In conclusion, the synthesized water-soluble diSe-SO₄ provides a H₂O₂-responsive ionic cross-linking material with a high cell affinity.