Application of polymeric nanomaterials in acute kidney injury therapy: from smart delivery to precision therapy

The prevention and treatment of acute kidney injury (AKI) remains a significant clinical challenge. Polymer nanomaterials, with their tunable physicochemical properties, offer a strategy for constructing efficient and intelligent drug delivery systems; however, there is currently a lack of systematic guidance for designing polymer carriers based on the pathophysiology of AKI. Unlike reviews that extensively survey various nanomaterials, this review focuses exclusively on polymer nanomaterials and constructs a correlative framework between carrier design and the dynamic pathological barriers of AKI, covering the size limitations of the damaged glomerular filtration barrier and non-glomerular entry pathways. This review classifies natural and synthetic polymers, elucidating their complementary advantages and emerging hybrid strategies that combine synthetic controllability with natural bioaffinity; it discusses the shift in targeting strategies from traditional receptor-mediated targeting to structure-driven adaptive targeting and introduces intelligent platforms such as reactive oxygen species/pH-responsive polymers, polymer nanozymes, and carbonized polymer dots; it also explores methods for integrating subtype-discriminating probes to address the etiological heterogeneity of AKI, facilitating the transition from intelligent delivery to precision therapy. Finally, we discuss the translational challenges and future research directions concerning AKI regarding biosafety and etiological heterogeneity. This review provides a reference for the development of safer and more effective polymer-based nanotherapeutics for AKI.