Targeting Kidney Fibrosis with Polymeric Nanocarriers

Chronic kidney disease (CKD) presents a significant health challenge, affecting nearly 10% of the global population. The management of CKD is hampered by the lack of drugs and drug delivery systems that specifically target the pathways, cells, and compartments involved in driving disease progression. We therefore set out to study the kidney targeting potential of polymeric nanocarriers based on poly­(N-(2-hydroxypropyl)­methacrylamide) (p­(HPMA)) in mice with unilateral ischemia-reperfusion-induced kidney fibrosis. Multimodal and multiscale optical imaging was employed to assess the kidney accumulation of six dye-labeled polymers differing in size and charge (7 and 32 kDa; neutral, negative, and positive) upon intravenous and subcutaneous administration. Particularly, the negatively charged 32 kDa polymeric nanocarrier was found to target diseased kidneys effectively, having a fibrosis-to-healthy kidney accumulation ratio of 4.0 ± 0.5 at 72 h post injection. Fluorescence microscopy showed that this polymer is predominantly retained within renal tubular cells. These findings unlock the potential of exploring p­(HPMA)-based polymeric nanocarriers for kidney-targeted drug delivery and CKD treatment.