Kidney Week

Abstract: SA-PO326

Development of a Glomerular Specific Targeting System with Perfluorocarbon Nanoparticles

Session Information

• Cellular Crosstalk in Glomerular Diseases - II
  October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1201 Glomerular Diseases: Fibrosis and Extracellular Matrix

Authors

• Wei, Jin, USF, Tampa, Florida, United States

Jin Wei,

• Grabau, Ryan, USF, Tampa, Florida, United States

Ryan Grabau,

• Zhang, Jie, USF, Tampa, Florida, United States

Jie Zhang,

• Wang, Lei, USF, Tampa, Florida, United States

Lei Wang,

• Wickline, Samuel, USF, Tampa, Florida, United States

Samuel Wickline,

• Pan, Hua, USF, Tampa, Florida, United States

Hua Pan,

• Liu, Ruisheng, University of South Florida College of Medicine , Tampa, Florida, United States

Ruisheng Liu,

Background

Perfluorocarbon (PFC) nanoparticles (NPs) are primarily limited to intravascular space. Glomerular basement membrane (GBM) is the only site where collagen IV (Col4) has direct contact with blood via fenestrated capillary endothelium. Our goal is to develop a novel Col4-targeted PFC NP that selectively targets kidney glomeruli as a local therapeutic vehicle.

Methods

Col4 -targeted PFC NPs were formulated by coupling PFC NPs to a Col4-targeting ligand. The binding specificity and efficiency of the Col4 -targeted NPs were evaluated on Col4 coated plate surfaces, in vitro with primary glomerular endothelial cells and mesangial cells, and in vivo in C57BL/6 mice.

Results

Rhodamine labeled Col4 targeted or non-targeted PFC NPs were applied in Col4 pre-coated 96 wells plate at stepwise doses (1, 2, 5, 10 and 20 ul/ml). The binding affinity was determined by fluorescence intensity with IVIS. The wells incubated with Col4 targeted PFC NPs showed a dose dependent increase in fluorescence as radiant efficiency e¹⁰ (0.37 ± 0.03, 0.51 ± 0.05, 1.33 ± 0.07, 2.38 ± 0.19, 2.71 ± 0.28). Minimal non-specific binding appeared. To evaluate the targeting properties in vitro, 1ul/ml rhodamine labeled Col4 targeted or non-targeted PFC NPs were applied on glomerular endothelial cells and mesangial cells. Significant cellular uptake of the Col4 targeted PFC NPs was observed, while it was not detectable in the cells incubated with non-targeted NPs. To evaluate the targeting properties in vivo, C57BL/6 mice were treated i.v. with 100ul rhodamine labeled Col4 targeted or non-targeted PFC NPs. Col4 targeted PFC NPs localized to glomeruli in the kidney sections, whereas non-targeted PFC NPs were undetectable, as shown in Figure.

Conclusion

We have designed PFC nanoparticles that selectively target glomeruli by binding to Col4 of GBM.

Funding

• NIDDK Support