한빛사 논문
Homan Kang, Sunghoon Rho, Wesley R. Stiles, Shuang Hu, Yoonji Baek, Do Won Hwang, Satoshi Kashiwagi, Moon Suk Kim,* and Hak Soo Choi*
Dr. H. Kang, S. Rho, W. R. Stiles, Dr. S. Hu, Y. Baek, Prof. D. W. Hwang, Prof. S. Kashiwagi, Prof. H. S. Choi
Gordon Center for Medical Imaging Department of Radiology Massachusetts General Hospital and Harvard Medical School Boston, MA 02114, USA
Prof. M. S. Kim
Department of Molecular Science and Technology Ajou University Suwon 16499, South Korea
*Corresponding author.
Abstract
Passive targeting of large nanoparticles by the enhanced permeability and retention (EPR) effect is a crucial concept for solid tumor targeting in cancer nanomedicine. There is, however, a trade-off between the long-term blood circulation of nanoparticles and their nonspecific background tissue uptake. To define this size-dependent EPR effect, near-infrared fluorophore-conjugated polyethylene glycols (PEG-ZW800s; 1–60 kDa) are designed and their biodistribution, pharmacokinetics, and renal clearance are evaluated in tumor-bearing mice. The targeting efficiency of size-variant PEG-ZW800s is investigated in terms of tumor-to-background ratio (TBR). Interestingly, smaller sized PEGs (≤20 kDa, 12 nm) exhibit significant tumor targeting with minimum to no nonspecific uptakes, while larger sized PEGs (>20 kDa, 13 nm) accumulate highly in major organs, including the lungs, liver, and pancreas. Among those tested, 20 kDa PEG-ZW800 exhibits the highest TBR, while excreting unbound molecules to the urinary bladder. This result lays a foundation for engineering tumor-targeted nanoparticles and therapeutics based on the size-dependent EPR effect.
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