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• W3036760068 endingPage "365" @default.
• W3036760068 startingPage "354" @default.
• W3036760068 abstract "The development of neuropharmaceutical gene delivery systems requires strategies to obtain efficient and effective brain targeting as well as blood-brain barrier (BBB) permeability. A brain-targeted gene delivery system based on a transferrin (Tf) and cell-penetrating peptide (CPP) dual-functionalized liposome, CPP-Tf-liposome, was designed and investigated for crossing BBB and permeating into the brain. We selected three sequences of CPPs [melittin, Kaposi fibroblast growth factor (kFGF), and penetration accelerating sequence–R8] and compared their ability to internalize into the cells and, subsequently, improve the transfection efficiency. Study of intracellular uptake indicated that liposomal penetration into bEnd.3 cells, primary astrocytes, and primary neurons occurred through multiple endocytosis pathways and surface modification with Tf and CPP enhanced the transfection efficiency of the nanoparticles. A coculture in vitro BBB model reproducing the in vivo anatomophysiological complexity of the biologic barrier was developed to characterize the penetrating properties of these designed liposomes. The dual-functionalized liposomes effectively crossed the in vitro barrier model followed by transfecting primary neurons. Liposome tissue distribution in vivo indicated superior ability of kFGF-Tf-liposomes to overcome BBB and reach brain of the mice after single intravenous administration. These findings demonstrate the feasibility of using strategically designed liposomes by combining Tf receptor targeting with enhanced cell penetration as a potential brain gene delivery vector. <h3>SIGNIFICANCE STATEMENT</h3> Rational synthesis of efficient brain-targeted gene carrier included modification of liposomes with a target-specific ligand, transferrin, and with cell-penetrating peptide to enhance cellular internalization. Our study used an in vitro triple coculture blood-brain barrier (BBB) model as a tool to characterize the permeability across BBB and functionality of designed liposomes prior to in vivo biodistribution studies. Our study demonstrated that rational design and characterization of BBB permeability are efficient strategies for development of brain-targeted gene carriers." @default.
• W3036760068 created "2020-06-25" @default.
• W3036760068 creator A5019359010 @default.
• W3036760068 creator A5035758532 @default.
• W3036760068 creator A5038413093 @default.
• W3036760068 creator A5040659202 @default.
• W3036760068 date "2020-06-19" @default.
• W3036760068 modified "2023-10-02" @default.
• W3036760068 title "Dual-Modified Liposome for Targeted and Enhanced Gene Delivery into Mice Brain" @default.
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• W3036760068 doi "https://doi.org/10.1124/jpet.119.264127" @default.
• W3036760068 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7430450" @default.
• W3036760068 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/32561686" @default.
• W3036760068 hasPublicationYear "2020" @default.
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