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Nano Research

, Volume 11, Issue 10, pp 5584–5595 | Cite as

Design and in vivo characterization of kidney-targeting multimodal micelles for renal drug delivery

  • Jonathan Wang
  • Christopher Poon
  • Deborah Chin
  • Sarah Milkowski
  • Vivian Lu
  • Kenneth R. Hallows
  • Eun Ji Chung
Research Article

Abstract

One in three Americans is at risk for developing chronic kidney disease (CKD) and end-stage renal disease (ESRD), leading to the need for dialysis or a kidney transplant. Small-molecule drugs have been proposed as therapies to manage kidney diseases, but high dosages are often required to achieve therapeutic efficacy, generating off-target side effects, some of which are lethal. To address these limitations, we developed a novel, kidney-targeting multimodal micelle (KM) system for drug delivery applications. Specifically, we incorporated the kidney-targeting peptide (Lysine-Lysine-Glutamic acid-Glutamic acid-Glutamic acid)3-Lysine) ((KKEEE)3K) into micelles. This peptide binds to megalin, a multi-ligand cell surface receptor present on renal tubule cells. When incubated with human kidney proximal tubule cells, KMs were found to be biocompatible in vitro. In vivo, KMs showed higher accumulation in the kidneys as compared to a non-targeted (NT) control upon intravenous injection in wild-type C57BL/6J mice. Histological evaluation showed no signs of tissue damage, while blood urea nitrogen (BUN) and creatinine levels were within normal ranges, validating the preservation of kidney health upon micelle administration. To our knowledge, this is the first utilization of (KKEEE)3K in a nanoparticle formulation, and our study offers strong evidence that this novel nanoparticle platform can be used as a candidate drug delivery carrier to direct therapeutics to diseased tissue in CKD.

Keywords

micelle kidney disease renal targeting biodistribution nanoparticle 

Notes

Acknowledgements

The authors would like to acknowledge the financial support from the University of Southern California (USC) Provost Fellowship awarded to J. W., the National Heart, Lung, and Blood Institute (NHLBI), R00HL124279 awarded to E. J. C., and the U.S. Dept. of Defense grant W81XWH-15-1-0420 to K. R. H. The authors also would like to thank the Center for Electron Microscopy and Microanalysis (CEMMA) at USC for assistance in TEM imaging.

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Copyright information

© Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Jonathan Wang
    • 1
  • Christopher Poon
    • 1
  • Deborah Chin
    • 1
  • Sarah Milkowski
    • 1
  • Vivian Lu
    • 1
  • Kenneth R. Hallows
    • 2
    • 3
  • Eun Ji Chung
    • 1
    • 2
    • 4
    • 5
    • 6
  1. 1.Department of Biomedical EngineeringUniversity of Southern CaliforniaLos AngelesUSA
  2. 2.Division of Nephrology and Hypertension, Department of Medicine, Keck School of MedicineUniversity of Southern CaliforniaLos AngelesUSA
  3. 3.USC/UKRO Kidney Research Center, Keck School of MedicineUniversity of Southern CaliforniaLos AngelesUSA
  4. 4.Norris Comprehensive Cancer CenterUniversity of Southern CaliforniaLos AngelesUSA
  5. 5.Department of Stem Cell Biology and Regenerative MedicineUniversity of Southern CaliforniaLos AngelesUSA
  6. 6.Mork Family Department of Chemical Engineering and Materials ScienceUniversity of Southern CaliforniaLos AngelesUSA

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