Disulfide proteinoid micelles responsive to reduction

Abstract

Proteinoid composed of aspartic acid (Asp) and Leucine (Leu) (Prot(Asp-Leu)) and of Asp, Leu, and dithiopropionic acid (DTPA) (Prot(Asp-Leu-DTPA)) were prepared by melt-condensation method. 1H NMR spectroscopy confirmed the successful synthesis of the proteinoids. The air/water interfacial tension of Prot(Asp-Leu-DTPA) solution increased when dithiothreitol (DTT, a reducing agent) was in the solution, possibly due to the breakdown of the disulfide bond of the proteinoid. On transmission electron micrograph, the proteinoid micelles were round and the diameter was less than 200 nm. Sulfur signal was found in the energy-dispersive X-ray spectrum of Prot(Asp-Leu-DTPA) micelle, indicating that the disulfide compound (i.e., DTPA) was successfully included in the proteinoid. As the pH value increased, the mean hydrodynamic diameter of the proteinoid micelle increased. The release degree of doxorubicin (DOX) loaded in Prot(Asp-Leu-DTPA) micelle was relatively low (3.5%–5.8%) and it was not affected by a reducing agent (i.e., DTT), possibly because of electrostatic attraction between DOX and the proteinoid. DTT had a significant effect on the release degree of amaranth (a negatively charged dye) loaded in Prot(Asp-Leu-DTPA) micelle. Prot(Asp-Leu-DTPA) has disulfide bonds so it can be broken into thiol proteinoids via DTT-caused reduction, giving rise to the micellar shell loosening and the promoted release.