Oxygen Permeable Dextran Nanogels as a Hemoglobin-Based Oxygen Carrier

Hemoglobin-based oxygen carriers have been extensively explored as oxygen delivery platform. Among them, encapsulation-based hemoglobin-based oxygen carriers face a key limitation: Dense matrices surrounding hemoglobin hinder the precise control of oxygen binding and release, thereby reducing oxygen delivery efficiency to target tissues. In this study, we developed a hemoglobin-loaded dextran-based nanogel (Hb@Dex-NG) via Schiff base cross-linking between oxidized dextran and 4-arm polyethylene glycol (PEG)-NH₂ to address these limitations. This nanogel system constructed via cross-linking of oxidized dextran and PEG features a permeable internal structure that enables efficient oxygen exchange. Ultraviolet-visible spectroscopy and oxygen dissociation analyses confirmed that the encapsulated hemoglobin retained oxygen-binding capacity. Notably, increasing the PEG content during synthesis led to denser internal structure, which, in turn, slowed oxygen release rates-demonstrating the modulability of this system as a controllable oxygen delivery carrier. Moreover, Hb@Dex-NG exhibited markedly reduced nitric oxide scavenging activity and suppressed autoxidation, suggesting enhanced vascular compatibility and oxidative stability. Overall, Hb@Dex-NG offers a structurally adjustable and biocompatible platform that overcomes major challenges associated with encapsulation strategy of oxygen delivery carrier, presenting a promising candidate for safe and effective oxygen delivery platforms.