Abstract: FR-PO991

Mesoscale Nanoparticles Selectively and Safely Target Renal Proximal Tubules

Session Information

Category: Bioengineering and Informatics

  • 101 Bioengineering and Informatics

Authors

  • Williams, Ryan M., Memorial Sloan Kettering Cancer Center, New York, New York, United States
  • Shah, Janki, Memorial Sloan Kettering Cancer Center, New York, New York, United States
  • Chen, Xi, Weill Cornell Medical College, New York, New York, United States
  • Jaimes, Edgar A., Memorial Sloan Kettering Cancer Center, New York, New York, United States
  • Heller, Daniel A, Memorial Sloan Kettering Cancer Center, New York, New York, United States
Background

Acute kidney injury accounts for 1% of hospital admissions in the US and over 20 million US adults (~11%) have chronic kidney disease. To address this problem, we developed mesoscale nanoparticles (MNPs) to selectively deliver therapies to the renal proximal tubules.

Methods

We synthesized MNPs from a biocompatible polymer (PLGA-PEG) to encapsulate a fluorescent dye for biodistribution and toxicology studies. Particles exhibited a size of approximately 400 nm and a negative surface charge. In vivo fluorescence imaging of mice determined the extent of renal localization via varying administration routes and doses. We used intravital and ex vivo fluorescence confocal microscopy to determine tissue-level distribution of MNPs. Finally, we performed toxicology experiments in mice via histology, blood counts, and renal biochemical panels to ascertain the safety of the particles up to one month in mice.

Results

We found that via intravenous administration, MNPs selectively localize to the kidneys up to 25-fold more than any other organ, uniquely selective among drug carrier systems. Within the kidneys, the localization was primarily to the proximal tubular epithelial cells, which is also novel to this system. Further, we found that these particles degrade and release their payload over weeks while they cause no renal or systemic toxicity.

Conclusion

Together, these results portend the pre-clinical development of therapeutic nanoparticles that are highly selective, safe, and provide long-term drug release with a single intravenous dose to treat renal diseases such as AKI and CKD.

a) Electron micrograph of MNPs. b) MNP localization to the kidneys. c) Relative renal MNP localization with varying IV doses. d) Tubular localization of MNPs (green is macrophages, red is MNPs). e) Serum BUN of mice treated with MNPs or control. f) Histology of kidneys in control or mice treated with MNPs.

Funding

  • Other NIH Support