Redox Sensitive Self-Assembling Dipeptide for Sustained Intracellular Drug Delivery.

Area of Science:

• Supramolecular Chemistry
• Biomaterials Science
• Nanotechnology

Background:

• Designing functional supramolecular assemblies remains challenging.
• Biocompatible self-assembled nanostructures are preferred for medical applications.
• Natural building blocks offer advantages in biocompatibility.

Purpose of the Study:

• To report the first redox-responsive dipeptide self-assembly into vesicles.
• To investigate the self-assembly mechanism and drug delivery capabilities.
• To explore the potential of peptide-based carriers for chemotherapy.

Main Methods:

• Synthesis of a redox-responsive dipeptide.
• Characterization of self-assembled vesicles in aqueous medium.
• All-atom molecular dynamics (MD) simulations to elucidate assembly mechanism.
• Doxorubicin (DOX) loading and in vitro release studies.
• Cellular uptake studies in MDA-MB-231 and HeLa cells.

Main Results:

• A simple dipeptide self-assembles into vesicles via π-π interactions of tryptophan residues.
• Peptide vesicles exhibit a DOX loading capacity of ~16% (w/w).
• Redox-triggered controlled release of DOX was observed.
• Drug-loaded vesicles successfully penetrated cancer cells and released payload.
• Vesicles disassembled intracellularly due to glutathione (GSH), releasing degradable dipeptides.

Conclusions:

• Minimalistic peptide design enables formation of drug-encapsulating vesicles.
• Redox-responsive peptide vesicles show potential as targeted drug delivery vehicles.
• Intracellular disassembly and degradability enhance safety and efficacy profile.