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Overcoming Hurdles in Nanoparticle Clinical Translation: The Influence of Experimental Design and Surface Modification

Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND 58105, USA
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Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(23), 6056; https://doi.org/10.3390/ijms20236056
Received: 9 October 2019 / Revised: 11 November 2019 / Accepted: 23 November 2019 / Published: 30 November 2019
(This article belongs to the Special Issue Surface-Functionalized Nanoparticles as Drug Carriers)
Nanoparticles are becoming an increasingly popular tool for biomedical imaging and drug delivery. While the prevalence of nanoparticle drug-delivery systems reported in the literature increases yearly, relatively little translation from the bench to the bedside has occurred. It is crucial for the scientific community to recognize this shortcoming and re-evaluate standard practices in the field, to increase clinical translatability. Currently, nanoparticle drug-delivery systems are designed to increase circulation, target disease states, enhance retention in diseased tissues, and provide targeted payload release. To manage these demands, the surface of the particle is often modified with a variety of chemical and biological moieties, including PEG, tumor targeting peptides, and environmentally responsive linkers. Regardless of the surface modifications, the nano–bio interface, which is mediated by opsonization and the protein corona, often remains problematic. While fabrication and assessment techniques for nanoparticles have seen continued advances, a thorough evaluation of the particle’s interaction with the immune system has lagged behind, seemingly taking a backseat to particle characterization. This review explores current limitations in the evaluation of surface-modified nanoparticle biocompatibility and in vivo model selection, suggesting a promising standardized pathway to clinical translation. View Full-Text
Keywords: nanoparticle clearance; surface modifications; protein corona; animal model selection nanoparticle clearance; surface modifications; protein corona; animal model selection
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Shreffler, J.W.; Pullan, J.E.; Dailey, K.M.; Mallik, S.; Brooks, A.E. Overcoming Hurdles in Nanoparticle Clinical Translation: The Influence of Experimental Design and Surface Modification. Int. J. Mol. Sci. 2019, 20, 6056.

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