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Cyclic Peptides KS-133 and KS-487 Multifunctionalized Nanoparticles Enable Efficient Brain Targeting for Treating
Kotaro Sakamoto1, Seigo Iwata2, Zihao Jin3,4
1Research & Development Department, Ichimaru Pharcos Company Limited, 318-1 Asagi, Motosu, 501-0475 Gifu, Japan.
JACS Au
|August 30, 2024
Summary
Researchers developed a novel nanoparticle drug delivery system targeting the brain for schizophrenia treatment. This system successfully delivered a drug to the brain and improved cognitive function in mouse models.
Area of Science:
- Neuroscience
- Biotechnology
- Pharmacology
Background:
- Central nervous system diseases require effective drug delivery systems to the brain.
- Vasoactive intestinal peptide receptor 2 (VIPR2) is a drug target for schizophrenia.
- Low-density lipoprotein receptor-related protein 1 (LRP1) facilitates blood-brain barrier crossing.
Purpose of the Study:
- To develop a novel drug delivery system (DDS) for treating schizophrenia.
- To utilize KS-487 as a brain-targeting peptide and KS-133 as the therapeutic agent.
- To evaluate the efficacy of a multifunctionalized multipeptide nanoparticle in inhibiting VIPR2.
Main Methods:
- Conjugation of dibenzocyclooctyne-KS-487 with N3-indocyanine green (ICG) via click reaction.
- Preparation of nanoparticles (NPs) encapsulating ICG and displaying KS-487.
- Subcutaneous administration of KS-133/KS-487 NPs to mouse models of schizophrenia.
Main Results:
- Fluorescence imaging confirmed ICG presence in mouse brains after intravenous administration.
- Subcutaneous administration of NPs led to significant ICG accumulation in the brain.
- Pharmacokinetic analysis showed time-dependent brain transport of KS-133.
- KS-133/KS-487 NPs significantly improved cognitive dysfunction in schizophrenia mouse models.
Conclusions:
- This study demonstrates the first potential therapeutic efficacy of a multifunctionalized multipeptide NP for inhibiting VIPR2.
- The developed DDS shows promise for treating schizophrenia by enabling targeted drug delivery to the brain.
- The novel nanoparticle system facilitates brain penetration and therapeutic agent delivery for CNS disorders.
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