A Natural Remedy: Kidney-Targeting Nanoplatform for Photoacoustic Imaging-Guided Three-in-one Theranostics of Rhabdomyolysis-induced Acute Kidney Injury

The high lethality of acute kidney injury (AKI) and the lack of safe and effective theranostic strategies pose significant challenges in clinical practice. Natural remedies are emerging as a promising alternative approach to alleviate AKI. Herein, we develop a novel kidney-targeting nanoplatform MNPC@SC, which engineered for pH-responsive drug release. Concretely, MNPC@SC encapsulates the natural bioactive ingredients curcumin (Cur) and melanin nanoparticles (MNPs) within a sialic acid (SA)-crosslinked chitosan shell, ensuring active renal targeting and optimal drug delivery via the electrostatic interactions between SA and chitosan. The acidic microenvironment of AKI triggers the responsive degradation of the MNPC@SC, further enabling the controlled release of MNPs and Cur specifically within the injured kidneys. The released MNPs and Cur achieve highly effective anti-inflammatory, anti-apoptotic, and anti-oxidant treatment, while MNPs serves as a contrast agent for photoacoustic (PA) imaging to self-monitor the drug distribution. To sum up, this pH-responsive targeting nanoplatform MNPC@SC, as a new natural remedy, is believed to achieve efficient PA imaging-guided three-in-one synergistic therapy for AKI, which may pave the way for exploring highly efficient and safe theranostic strategies for severe kidney injury. A kidney-targeting nanoplatform, MNPC@SC, is developed for pH-responsive release of natural curcumin and melanin in the acidic AKI microenvironment. It offers a triple-action therapy (anti-inflammatory, antioxidant, anti-apoptotic) and self-monitored photoacoustic imaging via melanin, constituting a natural theranostic strategy against AKI.