# Peptide-Engineered Seliciclib Nanomedicine for Brain-Targeted Delivery and Neuroprotection

## TL;DR

Researchers developed a brain-targeted nanomedicine using a peptide-modified delivery system to improve the neuroprotective effects of seliciclib.

## Contribution

A novel peptide-modified nanoparticle system was developed to enhance seliciclib delivery across the blood-brain barrier.

## Key findings

- Peptide-modified nanoparticles showed significantly greater translocation across a bEnd.3 cell monolayer.
- Peptide-conjugated nanoparticles accumulated 3.38-fold more in the brain compared to unmodified nanoparticles.
- The modified nanoparticles demonstrated significant neuroprotection against MPP⁺ in SH-SY5Y cells.

## Abstract

Seliciclib, a cyclin-dependent kinase 5 (CDK5) inhibitor, has demonstrated neuroprotective potential. However, its therapeutic application is limited by poor permeability across the blood–brain barrier (BBB). In this study, polymeric nanoparticles (NPs) modified with a BBB-targeting peptide ligand (His-Ala-Ile-Tyr-Pro-Arg-His) were employed to encapsulate seliciclib. In vitro transport studies showed that the peptide-modified NPs exhibited significantly greater translocation across a bEnd.3 cell monolayer compared to unmodified NPs. Furthermore, in vivo biodistribution analysis revealed that the brain accumulation of peptide-modified NPs was 3.38-fold higher than that of unmodified NPs. Notably, the peptide-conjugated, seliciclib-loaded NPs demonstrated a significant neuroprotective effect against the neurotoxin 1-methyl-4-phenylpyridinium (MPP⁺) in differentiated SH-SY5Y cells.