Self-Delivering Supramolecular Nanofiber Based on Peptide-Rhein Conjugate

A peptide-drug conjugate (PDC) is a single molecule formed by one or more drug molecules that are conjugated with functional short peptides. Some specially designed PDC can construct self-delivering supramolecular nanomedicine and improve the therapeutic effect. The design and synthesis of novel PDCs with unique assembly behavior are important for the drug delivery system. Rhein is a natural product extracted from rhubarb and has extensive pharmacological properties. In the present work, we successfully synthesized a novel PDC (VKVK-rhein) based on rhein through solid-phase synthesis technology and conventional coupling chemical methods. The anthraquinone structure of rhein and the structure of the short peptide (VKVK, Val-Lys-Val-Lys) provided VKVK-rhein with special assembly properties. VKVK-rhein can be assembled into supramolecular nanofibers in water. The equilibrium solubility, oil-water distribution coefficient, zeta potential, and cell viability of VKVK-rhein were systematically studied. Our work lays a foundation for further biological application of rhein-based PDCs.