Redox-sensitive self-assembled peptide nanocarriers for controlled drug delivery

Abstract

The most important point in the anticancer drug delivery system is to accurately deliver the loaded drug to the target tumor site and minimize side effects and systemic toxicity that may have to general healthy cells. To this end, many studies on stimuli responsive drug carriers such as pH, redox, and enzyme are being developed by utilizing the characteristics of cancer cell environments different from those around normal cells. The self-assembled peptide amphiphile (PA) nanovesicles are attracting attention in drug transport system due to their biocompatibility and hydrophilic and hydrophobic payload, so it can have dual loading capability. However, PA has difficulty in maintaining their stability in physiological media. Meanwhile, if the cell penetrating peptide is chemically introduced into PAs, the translocation activity of the self-assembled nanovesicle can be increased, thereby enhancing the intracellular access. In this thesis, I prepare GSH-triggered release of an anticancer drug from mono or bis disulfide crosslinkable PA nanovesicles consisting of a cell-penetrating TAT peptide. The PA 1 and 2, which are based on random-coil secondary structures and enable high drug loading, show different aqueous self-assembly behaviors. They constructed in vesicles and 2D sheets depending on the position of cysteine (C) in PA, even though they were made up of the same chemical building blocks. However, disulfide-linkage formation between the neighboring PAs using polar-aprotic DMF solvent lead to morphological transformation in the vesicle structures. Interestingly, the PA vesicles, as functions of disulfide position in assembly, showed significantly different drug loading capacities and efficiencies. Increase in the number of disulfide linkage between PAs (1-1) allowed the vesicular drug carriers to release sustainably anticancer drug to specific tumor sites. All PA vesicles shows a superior ability to transport anticancer drugs only to specific cancer cells. This study can provide a useful strategy for designing biocompatible PA vehicles for efficient drug delivery and could be a solid basis for the development of additional nanocarriers for biomedical applications.