Polydopamine-Coated Selenium Nanoparticles as a Stable Catalyst for Tunable and Sustained Nitric Oxide Generation.

Area of Science:

• Biomaterials Science
• Nanotechnology
• Medical Chemistry

Background:

• Nitric oxide (NO) is a crucial signaling molecule with therapeutic potential, but its clinical use is limited by instability and poor tissue penetration.
• Current strategies for NO delivery face challenges including short half-life and restricted diffusion, necessitating advanced delivery systems.
• Catalytic in situ NO generation from endogenous donors is a promising alternative, but existing catalysts like selenium nanoparticles (SeNPs) suffer from poor stability and pH sensitivity.

Purpose of the Study:

• To develop stable and pH-insensitive selenium-polydopamine core-shell nanoparticles (Se@PDA NPs) for effective nitric oxide (NO) generation.
• To enhance the catalytic stability and broaden the therapeutic pH range of selenium-based NO delivery systems.
• To investigate the biocompatibility, cellular uptake, and NO-releasing capabilities of Se@PDA NPs in relevant cellular models.

Main Methods:

• Synthesis of selenium-polydopamine core-shell nanoparticles (Se@PDA NPs) with tunable polydopamine (PDA) coating thickness.
• Evaluation of NO generation efficiency and stability across a wide pH range (5.5–8.5).
• Assessment of nanoparticle biocompatibility, cellular uptake in human coronary artery smooth muscle cells, and NO generation from endogenous S-nitrosothiols.

Main Results:

• Se@PDA NPs demonstrated consistent NO generation across a broad pH range (5.5–8.5), overcoming the pH sensitivity of bare SeNPs.
• The nanoparticles exhibited tunable NO release based on PDA coating thickness and showed enhanced cellular uptake and biocompatibility.
• Intracellular NO generation was observed in human coronary artery smooth muscle cells, leading to the formation of multicellular aggregates and indicating potential intercellular communication.
• Sustained NO release over multiple doses and long-term activity (at least two months) were confirmed.

Conclusions:

• Se@PDA NPs provide a stable, pH-tolerant platform for catalytic in situ NO generation, significantly improving upon existing selenium nanoparticle technologies.
• The enhanced biocompatibility, cellular uptake, and sustained NO release capabilities position Se@PDA NPs as a promising candidate for advanced NO-based therapeutic strategies.
• The observed promotion of multicellular aggregate formation suggests potential applications in modulating intercellular communication via NO signaling.