Discrete metal-based supramolecular structures for brain-targeted drug delivery

Overview

This research explores the development of discrete, metal-based supramolecular structures designed for brain-targeted drug delivery. Utilizing self-assembled [Pd2L4]4+ metal cages, these structures are engineered to encapsulate imaging components, such as the [99mTcO4]− anion, and are conjugated with BBB-translocating peptides like PepH3. This approach aims to improve the delivery and functionality of drugs and diagnostic agents across the blood-brain barrier, offering potential advancements in the treatment and diagnosis of brain diseases.

Technical specifications

• Structure: Self-assembled [Pd2L4]4+ metal cages with ligand L = 3,5-bis(3-ethynylpyridine)phenyl.
• Peptide Conjugation: Linked via a blood-brain barrier-translocating peptide synthesized using solid-phase peptide synthesis.
• Imaging Component: Encapsulation of the γ-emitting anion [99mTcO4]−.
• Validation: Future validation includes synthesis of a carboxylic ligand and peptide on a Rink Amide MBHA resin, followed by encapsulation and conjugation processes.
• Evaluation: Cytotoxicity will be assessed using MTT assays and the integrity of the BBB model evaluated with fluorescein isothiocyanate-dextran.

Technology readiness level

The technology is currently at TRL 2, indicating that it is in the early stages of experimental proof of concept. Further research and development are required to advance the readiness of these supramolecular structures for practical biomedical applications.