(591h) Hydrogen Sulfide Donor Micelles: Synthesis, Characterization and Therapeutic Potential

Hydrogen Sulfide Donor Micelles:
Synthesis, Characterization and Therapeutic Potential

Urara Hasegawa, André J. van der Vlies, Jerry J.Y. Chen, Tomoka Takatani-Nakase,
Ikuhiko Nakase

Hydrogen sulfide (H₂S) is produced in the human body and
serves as a gaseous signal-transmitter molecule that regulates inflammation,
relaxes vascular smooth muscles, promotes angiogenesis and mediates
neurotransmission. However, due to the difficulty in handling H₂S,
its therapeutic use has not been well explored. Therefore, development of H₂S
delivery technologies has attracted growing attention. One common approach is
to use H₂S donor compounds such as anethole dithiolethione (ADT)
derivatives which generate H₂S by the interaction with intracellular
enzymes. However, this approach suffers from uncontrolled gas generation which
limits their applications.

To address this issue, we developed
nano-sized gas donors based on polymeric micelles (H₂S donor
micelles, Figure 1) which enable sustained H₂S generation under
physiological conditions. In this presentation, we report the design and
synthesis of polymeric micelles containing anethole dithiolethione (ADT)
moieties. The micelles were prepared from amphiphilic diblock copolymers consisting
of a hydrophilic segment and a hydrophobic segment bearing ADT moieties. The micelles generated H₂S
slowly and continuously for sustained periods of time compared to the small H₂S
donor compound ADT. Since the disruption of the
micelles by adding a surfactant increased the rate of gas generation, the
micellar structure seems to be a key to successful control of gas generation. Furthermore,
the micelles showed various biological effects including pro-angiogenic and
anti-apoptotic effects in in vitro
cell culture assays as well as the chicken chorioallantoic membrane (CAM) model.

References

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Hasegawa, A. J. van der Vlies, Med. Chem.Comm.,
6 (2015) 273-276.