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Nitric oxide (NO) and hydrogen sulfide (H2S) are gaseous signalling molecules that regulate both physiological and pathological processes and have therapeutic promise for the treatment of many diseases. However, the intrinsic labile nature of therapeutic gases makes direct gas administration and regulated distribution at clinically relevant ranges challenging. Current gasotransmitter delivery systems load gasotransmitters directly or encapsulate gasotransmitter donors into delivering scaffolds. However, the storage capacity is limited by the finite storage capacity, necessitating continuous donor replenishment. These limitations drive a need to develop enzyme mimics that can locally and continuously catalyze endogenous prodrugs into gasotransmitters. This thesis focuses on the design, synthesis, and applications of nanozyme-based (nanoparticles with enzyme-like characteristics) gasotransmitter delivery vehicles. In this thesis, I first developed a copper-doped, zinc-based metal-organic framework (Cu2+/ZIF-8) for controlled NO generation from an endogenous NO donor, S-nitrosoglutathione (GSNO). NO generation was generated and regulated by adjusting copper doping percentages, nanozyme concentrations, and NO donor concentrations. The co-administration of Cu2+/ZIF-8 and GSNO resulted in a 45% reduction in Pseudomonas aeruginosa biofilm biomass, making them attractive candidates for antimicrobial applications. Following this success, I developed a catalyst/hydrogel system to co-deliver NO and H2S for potential biomedical applications. Before this, I investigated four different commercial H2S fluorescent probes in terms of their detection range, sensitivity, selectivity, and performance in varied conditions, accurately and sensitively in detecting H2S. Among the investigated probes, Washington State Probe-5 (WSP-5) was the most ideal H2S probe for its widest sensitivity linear range, low LOD, high selectivity and stability. Following this, a NO/H2S dual delivery platform was fabricated by loading a nonmetal-based catalyst, Se powder, into a biocompatible poly(vinyl alcohol) hydrogel, which demonstrated the capacity to generate NO and H2S in the presence of bio-abundant GSNO and Glutathione (GSH), simultaneously. Collectively, the findings in this thesis present the nanozyme- and catalyst-based biomaterials for NO and H2S release, highlighting their advances in gasotransmitter therapy and huge potential for the development of next-generation biomedical devices. |
