High Payload Dual Therapeutic-Imaging Nanocarriers for Triggered Tumor Delivery

Authors

  • Jin-Ki Kim,

    1. Division of Molecular Pharmaceutics, Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy and Lineberger, Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
    2. College of Pharmacy, Hanyang University, Ansan, Gyeonggi, 426-791, Republic of Korea
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  • Hong Yuan,

    1. Department of Radiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
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  • Jingxin Nie,

    1. Department of Radiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
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  • Yu-Tsai Yang,

    1. Division of Molecular Pharmaceutics, Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy and Lineberger, Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
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  • Markos Leggas,

    1. Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, Kentucky 40506, USA
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  • Philip M. Potter,

    1. Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA
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  • John Rinehart,

    1. Department of Medicine, University of Kentucky, Lexington, Kentucky 40506, USA
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  • Michael Jay,

    1. Division of Molecular Pharmaceutics, Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy and Lineberger, Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
    2. Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill/North, Carolina State University, Chapel Hill, North Carolina 27599, USA
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  • Xiuling Lu

    Corresponding author
    1. Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, Connecticut 06269, USA
    • Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, Connecticut 06269, USA.
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Abstract

The in vitro and in vivo characterization of an optimized formulation of nanoparticles (NPs) loaded with a high content of dexamethasone palmitate (DEX-P), a chemotherapeutic adjuvant that decreases interstitial fluid pressure in tumors, and 111In, a signaling agent, is described. These NPs are uniform in size and composition. Single photon emission computed tomography imaging demonstrates significant tumor uptake of 111In-labeled DEX-P NPs in tumor-bearing mice. As with many nanoparticle-based drug delivery systems, significant liver accumulation is observed. Assessment of liver histology and blood tests show no apparent hepatic or renal toxicity of the DEX-P NPs. Conversion of DEX-P to DEX occurs when DEX-P NPs are incubated with mouse plasma, human tumor homogenate and ascites from tumor bearing mice, but not with human plasma. This conversion is slower in plasma from Es1e(-/-)/SCID mice, a potential alternative animal model that better mimics humans; however, plasma from these mice are not completely devoid of esterase activity. The difference between blood and tumor esterase activity in humans facilitates the delivery of DEX-P NPs to tumors and the release of dexamethasone by an esterase trigger.

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