Abstract

Islet cell transplantation offers a promising therapeutic approach for type 1 diabetes by restoring endogenous, real-time blood glucose regulation. Despite its clinical potential, widespread application remains limited due to critical challenges such as donor scarcity, the need for lifelong immunosuppression, and significant graft loss caused by immediate blood-mediated inflammatory responses and ischemia/hypoxia at the transplantation site. To address these issues, we developed a novel nano‑oxygen delivery platform based on perfluorohexane/hemoglobin nanoparticles (PFH/Hb NPs). In this system, PFH enhances oxygen-carrying capacity while hemoglobin improves the biocompatibility of the perfluorinated core, enabling effective oxygen delivery within the hypoxic microenvironment. The PFH/Hb NPs synergistically alleviated oxidative stress and inflammatory responses, promoted early-stage neovascularization, and restored mitochondrial homeostasis by regulating fusion-fission dynamics. These effects collectively improved the survival and function of transplanted islets in vivo. This study provides a translationally relevant strategy to optimize graft microenvironments, offering new prospects for safer and more efficient minimally invasive islet transplantation to potentially cure diabetes.