title: Smart nanovehicles based on pH-triggered disassembly of supramolecular peptide-amphiphiles for efficient intracellular drug delivery.
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, SPAS is able to act as a smart NV to deliver its target to tumor cells using intracellular pH as a trigger. The DOX-loaded NVs are 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.
authors.affiliation: National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, Sichuan, 610064, PR China.
authors.forename: Xianghui
authors.initials: X
authors.lastname: Xu
authors.forename: Yunkun
authors.initials: Y
authors.lastname: Li
authors.forename: Haiping
authors.initials: H
authors.lastname: Li
authors.forename: Rong
authors.initials: R
authors.lastname: Liu
authors.forename: Mingming
authors.initials: M
authors.lastname: Sheng
authors.forename: Bin
authors.initials: B
authors.lastname: He
authors.forename: Zhongwei
authors.initials: Z
authors.lastname: Gu
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D016650:Fluorescein-5-isothiocyanate / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D018625:Microscopy, Atomic Force; D041681:NIH 3T3 Cells; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D010455:Peptides / Q000737:chemistry*; D013501:Surface-Active Agents / Q000737:chemistry*
chemical_list: D004337:Drug Carriers; D010455:Peptides; D013501:Surface-Active Agents; D004317:Doxorubicin; D016650:Fluorescein-5-isothiocyanate
keywords: controlled release; intracellular drug delivery; pH-triggered disassembly; smart nanovehicles; supramolecular peptide-amphiphiles