Journal
ADVANCED HEALTHCARE MATERIALS
Volume 9, Issue 1, Pages -Publisher
WILEY
DOI: 10.1002/adhm.201901223
Keywords
enhanced permeability and retention; pharmacokinetics; poly(ethylene glycol); renal clearance; tumor targeting
Funding
- National Institute of Biomedical Imaging and Bioengineering [R01EB022230]
- National Heart, Lung, and Blood Institute [R01HL143020]
- National Cancer Institute [R21CA223270]
- Creative Materials Discovery Program through the National Research Foundation of Korea [2019M3D1A1078938]
- National Research Foundation of Korea [21A20130000014] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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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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