In Vivo Transport of Renal Clearable Nanomedicines in Diseased Kidneys

Renal clearable nanomaterials have been considered promising nanomedicines for disease diagnosis and therapeutics. Understanding the in vivo transport of renal clearable nanomedicines under various diseased conditions is not only fundamentally important to unravelling pathophysiology in the nano regime, but also critical to successful translations of nanomedicines into the clinics. Since kidney disease as a silent killer influence more than 10% people in the world, understanding the transport mechanisms of renal clearable nanoparticles in the diseased kidneys will lay down a foundation for developing new disease diagnostics as well as treatments. This dissertation aims to unravel the in vivo transport of renal clearable nanomaterials in various kidney disease conditions, which includes seven chapters as follows. In Chapter 1, an overview is given to the current understandings of nanomedicines and their in vivo transport in normal and diseased kidney, which are classified into different categories according to its injury sites and pathologic mechanisms. In Chapter 2, we investigated the in vivo transport of PEG nanoparticles with different elimination pathways including glomerular filtration and renal tubular secretion in a well-known kidney disease model, cisplatin-induced kidney injury. In Chapter 3, we did a head-to-head comparison of the renal tubular secretion of PEG nanoparticle and small molecule, para-amino hippuric acid (PAH) in cisplatin-induced renal tubular injuries, and correlation between transport of the exogeneous probes and biomarkers was also investigated. In Chapter 4, we explored the feasibility of transcutaneous detection of cisplatin-induced acute kidney injury by combining fluorescent ICG-PEG45 and IRDye-PEG45 with a commercially available device. In Chapter 5, we studied the in vivo behaviors of various exogenous probes including the glomerular filtrated FITC-inulin and Au25SG18 and the renal tubular secreted PAH in cisplatin-injury acute kidney injury. In Chapter 6, we discussed the transport of nanoparticles in other types of kidney disease models including primary glomerular injuries induced by doxorubicin and tubular obstructions caused by folic acid. In Chapter 7, an outlook was given based on our current understandings of in vivo transport and interactions of nanomedicines in kidney diseases.