Abstract: SA-PO056
Size and Charge Effects of Nanoparticles for Renal Targeting in Polycystic Kidney Disease
Session Information
- Engineering-Based Approaches to Problems in Nephrology
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Bioengineering
- 300 Bioengineering
Authors
- Huang, Yi, University of Southern California, Los Angeles, California, United States
- Chung, Eun ji, University of Southern California, Los Angeles, California, United States
Background
Autosomal dominant polycystic kidney disease (ADPKD) is characterized by renal cyst formation and leads to ESRD. Tolvaptan, the only FDA approved treatment for ADPKD, has low bioavailability and results in non-specific uptake and liver toxicity. Our group has recently developed a novel nanoparticle system based on peptide amphiphile micelles (PAM) with the kidney-targeting peptide, (KKEEE)3K (K3) (Wischnjow, 2016 and Wang, 2018). To improve the nanoparticle targeting efficiency, we incorporated and tested a variety of peptide sequences: (EEKKK)3E (E3), (KKEEE)2K (K2), (EEKKK)2E (E2), (KKEEE)K (K1), and (EEKKK)E (E1). K2, E2, K1, and E1 are shorter amino acid sequences that result in smaller nanoparticles to cross the filtration barrier easily and E3, E2, and E1 are positively-charged sequences to allow for binding to the negatively-charged glomerular basement membrane.
Methods
All peptides were synthesized on an automated peptide synthesizer, conjugated to DSPE-PEG2000, and purified and characterized by HPLC and mass spectrometry. Size and charge of nanoparticles were measured by dynamic light scattering and zeta potential. The in vivo renal targeting ability of Cy7-labeled nanoparticles was assessed by tail vein injection of kidney-targeting PAMs, non-targeting PAMs, or PBS in C57BL/6 mice models. Organs were excised and imaged for Cy7 and the fluorescence signal was quantified using the AMI imaging system.
Results
K3 micelles had the largest diameter of 15.4 nm with a negative charge of -17.04 mV, while E1 had the smallest size of 10.6 nm with a near-neutral charge of 0.1 mV. Ex vivo imaging results demonstrated all micelles accumulated in the kidneys to a greater extent than other organs, and K3 and E3 demonstrated the highest uptake although not statistically significant (Figure 1).
Conclusion
Our approach demonstrated that our library of kidney-targeting PAMs can accumulate in the kidney. Future studies will further optimize charge and size to understand nanoparticle structure-function relationships in the context of kidney uptake.
Funding
- Other NIH Support