Abstract
A novel type of nanovehicle (NV) based on stimuli-responsive supramolecular peptide-amphiphiles (SPAs, dendritic poly (L-lysine) non-covalently linked poly (L-leucine))is developed for intracellular drug delivery. To determine the pH-dependent mechanism, the supramolecular peptide-amphiphile system (SPAS)is investigated at different pH conditions using a variety of physical and chemical approaches. The pH-triggered disassembly of SPAS can be attributed to the disappearance of non-covalent interactions within SPAs around the isoelectric point of poly (L-leucine). SPAS is found to encapsulate guest molecules at pH 7.4 but release them at pH 6.2. In this way, SPASis able to act as a smart NV to deliver its target to tumor cells using intracellular pH as a trigger. The DOX-loaded NVsare approximately 150 nm in size. In vitro release profiles and confocal laser scanning microscopy (CLSM) images of HepG2 cells confirm that lower pH conditions can trigger the disassembly of NVs and so achieve pH-dependent intracellular DOX delivery. In vitro cytotoxicity of the DOX-loaded NVs to HepG2 cells demonstrate that the smart NVs enhance the efficacy of hydrophobic DOX. Fluorescence-activated cell sorting (FACS) and CLSM results show that the NVs can enhance the endocytosis of DOX into HepG2 cells considerably and deliver DOX to the nuclei.
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