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  • Review Article
  • Published:

Nanomedicines for renal disease: current status and future applications

Nature Reviews Nephrology volume 12, pages 738–753 (2016)Cite this article

Subjects

Key Points

  • Oncology has benefited greatly from nanotechnology research and investment, yielding important insights that are applicable to kidney nanomedicines

  • Nanocarriers have the potential to improve the pharmacokinetics, biodistribution, toxicity, and efficacy of drugs

  • Delivery and retention of nanomedicines in the kidney is challenging and requires a deep understanding of the renal barriers and effective engineering of nanoparticle size, shape, and surface chemistry

  • To improve drug efficacy and minimize systemic toxicity, nanomedicines can be targeted to distinct kidney cell types and/or to extracellular matrix components such as the glomerular basement membrane

  • Nanocarriers can deliver drugs, proteins, peptides and nucleic acids, and can facilitate the targeted delivery of genes or RNA interference molecules to treat kidney disorders for which the efficacy of current treatments is limited

  • Organ-on-a-chip kidneys can streamline the simultaneous screening and testing of nanomedicines in environments that mimic the kidney and accelerate translation of kidney-specific therapeutics

Abstract

Treatment and management of kidney disease currently presents an enormous global burden, and the application of nanotechnology principles to renal disease therapy, although still at an early stage, has profound transformative potential. The increasing translation of nanomedicines to the clinic, alongside research efforts in tissue regeneration and organ-on-a-chip investigations, are likely to provide novel solutions to treat kidney diseases. Our understanding of renal anatomy and of how the biological and physico-chemical properties of nanomedicines (the combination of a nanocarrier and a drug) influence their interactions with renal tissues has improved dramatically. Tailoring of nanomedicines in terms of kidney retention and binding to key membranes and cell populations associated with renal diseases is now possible and greatly enhances their localization, tolerability, and efficacy. This Review outlines nanomedicine characteristics central to improved targeting of renal cells and highlights the prospects, challenges, and opportunities of nanotechnology-mediated therapies for renal diseases.

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Figure 1: Nanoparticle composition and features.
Figure 2: The kidney glomerulus and the glomerular basement membrane in health and disease.
Figure 3: In vitro systems to test nanoparticles.

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Acknowledgements

O.C.F acknowledges support from the NHLBI HL127464, NCI CA151884, NIBIB EB015419 and the David Koch-Prostate Cancer Foundation Award in Nanotherapeutics. J.C.H is supported by NIH 1R01DK078897, NIH 1R01DK088541, NIH P01-DK-56492, Chinese 973 fund 2012CB517601.

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Authors and Affiliations

  1. Center for Nanomedicine and Department of Anaesthesiology, Brigham and Women's Hospital and Harvard Medical School, 75 Francis Street, Boston, 02115, Massachusetts, USA

    Nazila Kamaly & Omid C. Farokhzad

  2. Department of Micro and Nanotechnology, Technical University of Denmark, Produktionstorvet, Kgs. Lyngby, 2800, Denmark

    Nazila Kamaly

  3. Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, 10029, NY, USA

    John C. He

  4. Program in Membrane Biology and Division of Nephrology, Center for Assessment Technology and Continuous Health, and Center for Systems Biology, Simches Research Center, Massachusetts General Hospital, 55 Fruit Street, Boston, 02114, Massachusetts, USA

    Dennis A. Ausiello

  5. Department of Medicine, Harvard Medical School, 25 Shattuck Street, Boston, 02114, Massachusetts, USA

    Dennis A. Ausiello

  6. King Abdulaziz University, King Fahad Road, Jeddah, 22254, Saudi Arabia

    Omid C. Farokhzad

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  1. Nazila Kamaly
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All authors contributed to researching data for the article, discussion of the article's content, writing, and review or editing of the manuscript before submission.

Corresponding author

Correspondence to Omid C. Farokhzad.

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Competing interests

O.C.F. has financial interests in Selecta Biosciences, Tarveda Therapeutics, and Placon Therapeutics. D.A.A serves on the Board of Directors of Pfizer, Alnylam Pharmaceuticals, Seres Therapeutics, Tarveda Therapeutics and Placon Therapeutics. The other authors declare no competing interests.

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Glossary

Nanoparticles

Nanoscale particles with modifiable shape and charge capable of carrying a specific payload (drugs, diagnostic molecules etc.).

Colloid

Substance formed by a non-crystalline material (here nanomaterial) of either natural or synthetic origin dispersed in a solution.

Organ-on-a-chip

Microfluidic devices used to culture living cells under continuous perfusion in micorometer-sized chambers; they are primarily used to reproduce the physiological functions of tissues and organs as closely as possible.

PEGylation

Attachment of polyethers to the surface of nanoparticles in order to minimize unwanted interactions with their biological surroundings.

Cmax

Maximal serum concentration of a drug or nanoparticle achievable after administration.

Top-down fabrication method

Synthesis of a structure by etching or removal of material from a template or substrate to achieve specific shapes or sizes.

Particle replication in non-wetting templates

Fabrication technique whereby a pre-particle solution is distributed in a mould with nanosized cavities to generate nanoparticles with precisely defined shape, size, composition and surface properties.

Aspect ratio

Ratio of the width to the height of a nanoparticle.

Enhanced permeability and retention (EPR) effect

Describes the accumulation and retention of colloidal nanoparticles within tumour tissue as a result of increased endothelial gap junction distances due to heterogeneous vessel formation and growth.

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Kamaly, N., He, J., Ausiello, D. et al. Nanomedicines for renal disease: current status and future applications. Nat Rev Nephrol 12, 738–753 (2016). https://doi.org/10.1038/nrneph.2016.156

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