Emerging concepts in dendrimer-based nanomedicine: from design principles to clinical applications

Authors

  • R. M. Kannan,

    1. Department of Ophthalmology, Center for Nanomedicine, Baltimore, MD, USA
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  • E. Nance,

    1. Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
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  • S. Kannan,

    1. Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
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  • D. A. Tomalia

    Corresponding author
    1. National Dendrimer & Nanotechnology Center, NanoSynthons LLC, Mt. Pleasant, MI, USA
    2. Department of Chemistry, University of Pennsylvania, Philadelphia, PA, USA
    3. Department of Physics, Virginia Commonwealth University, Richmond, VA, USA
    • Correspondence: Donald A. Tomalia PhD, National Dendrimer & Nanotechnology Center, NanoSynthons LLC, Mt. Pleasant, MI, USA (fax: 989-317-3737; e-mail: donald.tomalia@nanosynthons.com).

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Abstract

Dendrimers are discrete nanostructures/nanoparticles with ‘onion skin-like’ branched layers. Beginning with a core, these nanostructures grow in concentric layers to produce stepwise increases in size that are similar to the dimensions of many in vivo globular proteins. These branched tree-like concentric layers are referred to as ‘generations’. The outer generation of each dendrimer presents a precise number of functional groups that may act as a monodispersed platform for engineering favourable nanoparticle–drug and nanoparticle–tissue interactions. These features have attracted significant attention in medicine as nanocarriers for traditional small drugs, proteins, DNA/RNA and in some instances as intrinsically active nanoscale drugs. Dendrimer-based drugs, as well as diagnostic and imaging agents, are emerging as promising candidates for many nanomedicine applications. First, we will provide a brief survey of recent nanomedicines that are either approved or in the clinical approval process. This will be followed by an introduction to a new ‘nanoperiodic’ concept which proposes nanoparticle structure control and the engineering of ‘critical nanoscale design parameters’ (CNDPs) as a strategy for optimizing pharmocokinetics, pharmocodynamics and site-specific targeting of disease. This paradigm has led to the emergence of CNDP-directed nanoperiodic property patterns relating nanoparticle behaviour to critical in vivo clinical translation issues such as cellular uptake, transport, elimination, biodistribution, accumulation and nanotoxicology. With a focus on dendrimers, these CNDP-directed nanoperiodic patterns are used as a strategy for designing and optimizing nanoparticles for a variety of drug delivery and imaging applications, including a recent dendrimer-based theranostic nanodevice for imaging and treating cancer. Several emerging preclinical dendrimer-based nanotherapy concepts related to inflammation, neuro-inflammatory disorders, oncology and infectious and ocular diseases are reviewed. Finally we will consider challenges and opportunities anticipated for future clinical translation, nanotoxicology and the commercialization of nanomedicine.

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