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In vivo analysis reveals KS-487's superior blood-brain barrier penetration and selectivity compared to Angiopep-2, suggesting potential for drug delivery.
KS-487 is a cyclic peptide previously reported to bind low-density lipoprotein receptor-related protein 1 (LRP1) and exhibit blood-brain barrier (BBB) permeability. In this study, we evaluated the in vivo BBB permeability and selectivity of KS-487 in comparison with those of Angiopep-2 (ANG2), a widely used linear LRP1-binding peptide. Indocyanine green (ICG)-labeled KS-487 and ANG2 were subcutaneously administered to mice, and their biodistribution was assessed at 24, 48, and 72 h by using in vivo imaging. ICG-KS-487 and ICG-ANG2 displayed comparable brain permeability and nearly identical time-course profiles. Notably, ICG-KS-487 demonstrated greater brain selectivity, defined as the ratio of brain to liver accumulation at 72 h. No adverse effects, including weight loss or histopathological abnormalities in major organs, were observed in mice treated with ICG-KS-487. These findings highlight the remarkable brain-targeting properties and safety profile of KS-487, supporting its potential utility as a targeting ligand for drug delivery to treat brain-related disorders.
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Asukabe et al. (2025) studied this question.
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