Highly Thiolated Poly (Beta-Amino Ester) Nanoparticles for Acute Redox Applications

Area of Science:

• Biomaterials Science
• Polymer Chemistry
• Nanotechnology
• Oxidative Stress Research

Background:

• Disulfides are widely used for reversible cross-linking, easily reducing to thiols.
• The free-radical scavenging ability of reduced disulfides is often overlooked.
• Cellular reducing agents like glutathione protect against oxidative stress.

Purpose of the Study:

• To synthesize and characterize highly thiolated poly(β-amino ester) (PBAE) nanoparticles.
• To explore the potential of these nanoparticles as radioprotective agents.
• To investigate their antioxidant properties by mimicking cellular reducing chemistry.

Main Methods:

• Synthesis of degradation-tunable PBAE hydrogels with high cystamine content (up to 26 wt %).
• Reduction of disulfide-cross-linked hydrogels to yield soluble thiolated oligomers.
• Formulation of thiolated nanoparticles via single emulsion and characterization of their stability and thiol concentration.

Main Results:

• Successfully synthesized highly thiolated PBAE nanoparticles.
• Nanoparticles demonstrated size stability in phosphate-buffered saline.
• Achieved high thiol concentrations (11.0 ± 1.1 mM), comparable to cellular glutathione levels (1–10 mM).

Conclusions:

• The developed thiolated PBAE nanoparticles possess significant free-radical scavenging capacity.
• These nanoparticles can serve as effective conjugation platforms and potential radioprotective agents.
• The findings highlight the under-appreciated antioxidant role of reduced disulfide materials in nanoparticle formulations.