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, we designed near-infrared fluorophoreconjugated polyethylene glycols (PEG-ZW800s; 1-60 kDa) and evaluated their biodistribution, pharmacokinetics, and renal clearance in tumor-bearing mice. The targeting efficiency of sizevariant PEG-ZW800s was investigated in terms of tumor-to-background ratio (TBR). Interestingly, smaller sized PEGs (≤20 kDa, 12 nm) exhibited significant tumor targeting with minimum to no nonspecific uptakes, while larger sized PEGs (>20 kDa, 13 nm) accumulated highly in major organs, including the lungs, liver, and pancreas. Among those tested, 20 kDa PEG-ZW800 exhibited 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 sizedependent EPR effect.

Alzheimer’s disease (AD) is a neurodegenerative disease causing progressive cognitive decline until eventual death. AD affects millions of individuals worldwide in the absence of effective treatment options, and its clinical causes are still uncertain. The onset of dementia symptoms indicates severe neurodegeneration has already taken place. Therefore, AD diagnosis at an early stage is essential as it results in more effective therapy to slow its progression. The current clinical diagnosis of AD relies on mental examinations and brain imaging to determine whether patients meet diagnostic criteria, and biomedical research focuses on finding associated biomarkers by using neuroimaging techniques. Multiple clinical brain imaging modalities emerged as potential techniques to study AD, showing a range of capacity in their preciseness to identify the disease. This review presents the advantages and limitations of brain imaging modalities for AD diagnosis and discusses their clinical value.