title: Self-assembled Tat nanofibers as effective drug carrier and transporter.
abstract: Cell penetrating peptides (CPPs) have been extensively explored as molecular vectors through covalent linkage to anticancer drugs to improve the drug's water solubility and to help overcome multidrug resistance. We report here the use of the Tat CPP as a molecular building unit to construct well-defined supramolecular nanofibers that can be utilized as a nanoscale vector to encapsulate the hydrophobic drug paclitaxel (PTX) (loading efficiency: 89.7 ± 5.0%) with a high loading capacity (6.8 ± 0.4%). Notably, our TEM imaging results reveal that nanofibers containing a higher PTX content tend to be more flexible than those with a lower PTX content. Fluorescence and confocal microscopy imaging show that the Tat nanofibers can effectively transport encapsulated molecules into the cells through an adsorptive-mediated endocytosis pathway. Cytotoxicity experiments and flow cytometry measurements demonstrate that PTX loaded in the nanofibers exerts its cytotoxicity against cancer cells by arresting the cells at the G2/M phase, the same working mechanism as free PTX.
authors.affiliation: Department of Chemical and Biomolecular Engineering, and Institute for NanoBioTechnology, The Johns Hopkins University, Baltimore, Maryland 21218, USA.
authors.forename: Pengcheng
authors.initials: P
authors.lastname: Zhang
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Cheetham
authors.forename: Yi-An
authors.initials: YA
authors.lastname: Lin
authors.forename: Honggang
authors.initials: H
authors.lastname: Cui
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D004058:Diffusion; D004705:Endocytosis; D015696:Gene Products, tat / Q000737:chemistry*; D006801:Humans; D008422:Materials Testing; D053769:Nanocapsules / Q000008:administration & dosage* / Q000737:chemistry* / Q000648:ultrastructure; D057139:Nanofibers / Q000008:administration & dosage* / Q000737:chemistry* / Q000648:ultrastructure; D009374:Neoplasms, Experimental / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D015696:Gene Products, tat; D053769:Nanocapsules; D017239:Paclitaxel