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Tumoral accumulation of long-circulating, self-assembled nanoparticles and its visualization by gamma scintigraphy

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Abstract

The enhanced permeability and retention (EPR) effect is used extensively for the passive targeting of many macromolecular drugs for tumors. Indeed, the EPR concept has been a gold standard in polymeric anticancer drug delivery systems. This study investigated the tumoral distribution of self-assembled nanoparticles based on the EPR effect using fluorescein and radio-labeled nanoparticles. Self-assembled nanoparticles were prepared from amphiphilic chitosan derivatives, and their tissue distribution was examined in tumor-bearing mice. The size of the nanoparticles was controlled to be 330 nm, which is a size suited for opening between thedefective endothelial cells in tumors. The long-circulating polymer nanoparticles were allowed to gradually accumulate in the tumors for 11 days. The amount of nanoparticles accumulated in the tumors was remarkably augmented from 3.4%ID/g tissue at 1 day to 25.9%ID/g tissue at 11 days after i.v. administration. The self-assembled nanoparticles were sustained at a high level throughout the 14 day experimental period, indicating their long systemic retention in the blood circulation. The γ-images provided clear evidence of selective tumor localization of the131 I-labeled nanoparticles. Confocal microscopy revealed the fluorescein-labeled nanoparticles to be preferentially localized in the perivascular regions, suggesting their extravasation to the tumors through the hyperpermeable angiogenic tumor vasculature. This highly selective tumoral accumulation of nanoparticles was attributed to the leakiness of the blood vessels in the tumors and their long residence time in the blood circulation.

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Authors and Affiliations

  1. Department of Chemical Engineering, Hanyang University, 426-791, Ansan, Korea

    Yong Woo Cho

  2. Advanced Medical Technology Cluster for Diagnosis and Prediction, Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, 700-422, Daegu, Korea

    Yoo-Shin Kim, In-San Kim & Rang-Woon Park

  3. Asan Medical Center, University of Ulsan College of Medicine, 138-736, Seoul, Korea

    Seung Jun Oh, Dae Hyuk Moon & Sang Yoon Kim

  4. Biomedical Research Center, Korea Institute of Science and Technology, 136-791, Seoul, Korea

    Ick Chan Kwon

Authors
  1. Yong Woo Cho
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  2. Yoo-Shin Kim
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  4. Rang-Woon Park
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  5. Seung Jun Oh
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  6. Dae Hyuk Moon
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Correspondence to Rang-Woon Park.

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Cho, Y.W., Kim, YS., Kim, IS. et al. Tumoral accumulation of long-circulating, self-assembled nanoparticles and its visualization by gamma scintigraphy. Macromol. Res. 16, 15–20 (2008). https://doi.org/10.1007/BF03218955

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  • DOI: https://doi.org/10.1007/BF03218955

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