The influence of modified molecular (d/l-serine) chirality on the theragnostics of PAMAM-based nanomedicine for acute kidney injury

Abstract

Acute kidney injury (AKI) is a severe clinical disease with extremely high morbidity and mortality. It is challenging to find a simple method for early detection of AKI and monitoring the treatment results. Renal tubular damage and inflammation are early events in AKI. Renal tubular damage is conducive to the accumulation of small-sized nanoparticles in the kidney, and inflammation is related to the excessive production of H₂O₂. Recent studies proved that chiral molecule modification of nanomaterials is a powerful strategy to regulate their biodistribution. Thus, L-serine and D-serine modified poly(amidoamine) (PAMAM) dendrimers were synthesized and used as fluorescent probe (NPSH) carriers to obtain L-SPH and D-SPH, respectively. D-SPH has a strong accumulation capability in the kidney of AKI mice. Then, the H₂O₂ fluorescent probe can detect the excessively produced H₂O₂ to generate fluorescence to diagnose AKI. Subsequently, the anti-inflammatory drug manganese pentacarbonyl bromide (CORM) was loaded in D-SPH to obtain D-SPHC with AKI theragnostic functions. Simultaneously, the D-SPHC fluorescence signal intensity change during the treatment can be used to monitor the recovery process. This study is the first report of chiral materials used in the diagnosis and treatment of AKI.