# Nanotechnology, Nanomedicine, and the Kidney
## 5 Nanotechnology for Renal Therapy
### Drug Delivery
#### 5.1.2 Antibodies  
Biological enzymes, immunoglobulins, and peptide hormones are effective in targeting the kidney. Intra kidney delivery can be directed via immunoglobulin specificity or the uptake selectivity of peptides in different compartments.  
Complement activation is part of the immune response and provides an initial response against infections. The dysregulation of the activated complement system is a component in many renal diseases, such as glomerulopathies, ischemia/reperfusion injury, and thrombotic microangiopathies. Macrophage antigen 1 (Mac-1) is a receptor mediating complement-activated inflammation and is expressed predominantly on macrophages infiltrating sites of tissue damage and inflammation. Mac-1 consists of integrin aM (CD11b) and integrin 2 (CD18). [PERSON] et al., conjugated a CD11b antibody with silica nanoparticles. After injection in mice with experimental renal obstruction, he found that the antibody constructs bound with high affinity to the macrophages located to the area of tubular damage and interstitial inflammation [62].  
Renal endothelial cells are an important part of the renal filtration apparatus. They are the target of complement activated injury during transplant-associated ischemia, leading to a delayed posttransplant function. [PERSON] et al., generated an antibody specific for the complement factor C5 that was coupled with a cyclic RGD peptide [63]. The peptide RGD-4C has been found in a phage display assay to confer the binding to integrins expressed on endothelial cells. They found that in a rat model for I/R injury, the injected anti C5 antibody RGD conjugate was localized to the endothelial cells, where it prevented complement-activated injury. The antibody conjugate is proposed to be used in transplant medicine, where it could be used to pre-treat transplant organs from I/R associated injury.  
The podocytes, or glomerular visceral epithelial cells, are the final barrier of renal filtration and their function is essential to prevent proteinuria. They are injured in a wide array of immune and non-immune mediated diseases. To target the podocytes within the glomerulus, a podocyte-specific antibody was modified by enzymatic cleavage and conjugation of a protamine molecule. Protanine exhibits a positive surface charged and, thus, can bind negatively charged nucleic acids, such a siRNA. In addition, protamine protects nucleic acids from degradation. When this antibody, loaded with siRNA specific for nephrin, was injected into a rodent, the mRNA level for nephrin was significantly reduced [64], demonstrating the specificity of the approach.  
In a recent publication, [PERSON] et al., reported using an antibody F(ab')2 fragment to target Plasmalemma vesicle-associated protein (PV1), an endothelial cell-specific protein that is a structural component of fenestrations, caveolae, and trans-endothelial channels. PV-1 expression is increased during ischemic events. They developed a high-affinity anti-PV-1 antibody F(ab')\({}_{2}\) fragment that showed high affinity to the kidney and assessed kidney targeting and rapid excretion [65]. They found that anti-PV-1 antibody F(ab')\({}_{2}\) accumulated in the kidney, and 4 h after injection, the serum concentration of the anti-PV-1 antibody F(ab')\({}_{2}\) was 40x lower than an unspecific isotype control antibody that underwent rapid urinary elimination. They also found that a monovalent PV-1 (Fab-C4) antibody lost its kidney binding capacity. Their findings suggest that the anti-PV-1 antibody F(ab')\({}_{2}\) is potentially a useful drug carried to target the tubular cells of the kidney.