Engineering Bioactive Liposomal Nanoparticles for Kidney-Targeted ECFC Backpacks

Endothelial colony-forming cells (ECFCs) possess significant potential for vascular repair and kidney regeneration but face challenges in selective homing and retention within target tissues. Here, we present a strategy to enhance ECFC targeting to human renal proximal tubular epithelial cells by cell surface engineering with kidney-targeted liposomal nanoparticles conjugated via thiol-maleimide chemistry. These nanoparticles incorporate a targeting peptide that facilitates receptor-mediated binding to renal epithelial cells without altering ECFC phenotypes and cell viability. We demonstrate optimized nanoparticle conjugation and loading that maximizes cellular binding while preserving key progenitor phenotypes and cellular function. Furthermore, the modular nanoparticle design features tunable physicochemical properties conducive to renal targeting and minimal off-target interactions in comparison to fibroblasts. This approach establishes in vitro kidney cell selectivity of surface-engineered ECFCs, laying a foundation for precision nanotechnology to enhance biocompatibility and future organ-specific regenerative therapies.