LAUSR

Restoration of sufficient blood supply for the treatment of ischemia remains a significant scientific and clinical challenge. Here, we introduce a cell-like nanoparticle delivery technology that is capable of recapitulating multiple cell functions for the spatiotemporal triggering of vascular regeneration. Specifically, a copper-containing protein was successfully prepared using a recombinant protein scaffold based on a de novo design strategy, which facilitated the timely release of nitric oxide (NO) and improved accumulation of particles within ischemic tissues. Through closely mimicking physiological cues, we demonstrated the benefits of bioactive factors secreted from hypoxic stem cells on promoting angiogenesis. Following this cell-mimicking manner, artificial hybrid nano-sized cells (Hynocell) were constructed by integrating the hypoxic stem cell secretome into nanoparticles with surface coatings of cell membranes fused with copper-containing protein. The Hynocell, hybridized with different cell-derived components, provided synergistic effects on targeting ischemic tissues and promoting vascular regeneration in acute hindlimb ischemia and acute myocardial infarction models. This study offers new insights into the utilization of nanotechnology to potentiate the development of cell-free therapeutics. This article is protected by copyright. All rights reserved.