Browsing by Author "Hsieh, Tsung-Ying"

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Neurotensin-Conjugated Reduced Graphene Oxide with Multi-Stage Near-Infrared-Triggered Synergic Targeted Neuron Gene Transfection In Vitro and In Vivo for Neurodegenerative Disease Therapy
(2016-12)
Hsieh, Tsung-Ying
;
Huang, Wei-Chen
;
Kang, Yi-Da
;
Chu, Chao-Yi
;
Liao, Wen-Lin
Delivery efficiency with gene transfection is a pivotal point in achieving maximized therapeutic efficacy and has been an important challenge with central nervous system (CNS) diseases. In this study, neurotensin (NT, a neuro-specific peptide)-conjugated polyethylenimine (PEI)-modified reduced graphene oxide (rGO) nanoparticles with precisely controlled two-stage near-infrared (NIR)-laser photothermal treatment to enhance the ability to target neurons and achieve high gene transfection in neurons. First-stage NIR laser irradiation on the cells with nanoparticles attached on the surface can increase the permeability of the cell membrane, resulting in an apparent increase in cellular uptake compared to untreated cells. In addition, second-stage NIR laser irradiation on the cells with nanoparticles inside can further induce endo/lysosomal cavitation, which not only helps nanoparticles escape from endo/lysosomes but also prevents plasmid DNA (pDNA) from being digested by DNase I. At least double pDNA amount can be released from rGO-PEI-NT/pDNA under NIR laser trigger release compared to natural release. Moreover, in vitro differentiated PC-12 cell and in vivo mice (C57BL/6) brain transfection experiments have demonstrated the highest transfection efficiency occurring when NT modification is combined with external multi-stage stimuli-responsive NIR laser treatment. The combination of neuro-specific targeting peptide and external NIR-laser-triggered aid provides a nanoplatform for gene therapy in CNS diseases.
Surfactant-Free, Lipo-Polymersomes Stabilized by Iron Oxide Nanoparticles/Polymer Interlayer for Synergistically Targeted and Magnetically Guided Gene Delivery
(2014-02-01)
Hu, Shang-Hsiu
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Hsieh, Tsung-Ying
;
Chiang, Chin-Sheng
;
Chen, Po-Jung
;
Chen, You-Yin
Gene therapy holds promise to suppress carcinomas but still remains far removed from clinic because of the lack of a safe and effective delivery system. Besides enhancing transfection efficiency, the difficulty in gene therapy is how to deliver sufficient gene molecules to the site of interest. Herein, the rational design of surfactant-free lipo-polymersomes (LPPs) to overcome these problems is reported, simultaneously using a lipid-stabilized double emulsion approach. The LPPs are designed to conceal the cationic lipids and plasmid DNA inside the core along with iron oxide nanoparticles/polymer interlayer and a relatively neutral lipid shell to avoid the undesired interaction during circulation, leading to high accumulation in the tumors of mice. Furthermore, guided by an external magnetic field and the folic acid (FA) that target tumors via folate receptor-mediated endocytosis on the cell surface, the vectors demonstrate a 30-40-fold increase in cell uptake. Moreover, this synergistic tumor-targeted approach can enhance a 10-fold increase in in vivo transfection efficacy by promoting the delivery of LPPs to cancer cells and facilitating the endosomal escape of gene molecules. The new insights and capabilities represent a major step in nanovector engineering for safe and efficient gene delivery.