Surfactant-Free, Lipo-Polymersomes Stabilized by Iron Oxide Nanoparticles/Polymer Interlayer for Synergistically Targeted and Magnetically Guided Gene Delivery

• Published in: Advanced healthcare materials 2014-02, Vol.3 (2), p.273-282
• Main Authors: Hu, Shang-Hsiu, Hsieh, Tsung-Ying, Chiang, Chin-Sheng, Chen, Po-Jung, Chen, You-Yin, Chiu, Tsung-Lang, Chen, San-Yuan
• Format: Article
• Language: English
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Applied cell therapy and gene therapy; Biological and medical sciences; Cationic; Cross-disciplinary physics: materials science; rheology; Exact sciences and technology; Ferric Compounds - chemistry; gene delivery; Gene therapy; Gene Transfer Techniques; Genes; HeLa Cells; Humans; Interlayers; iron oxide nanoparticles; Iron oxides; Lipids; Materials science; Medical research; Medical sciences; nanocapsule; Nanocapsules - chemistry; Nanoparticles; Nanoparticles - chemistry; Nanoscale materials and structures: fabrication and characterization; Physics; Polymers - chemistry; Surface-Active Agents - chemistry; Surfactants; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; targeted; Technology. Biomaterials. Equipments; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Tumors
• ISSN: 2192-2640; 2192-2659
• DOI: 10.1002/adhm.201300122

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. Lipo‐polymersomes with cationic lipids and pDNA‐encapsulated are made via a surfactant‐free double‐emulsion approach. By incorporating iron oxide nanoparticles and tethering cell‐targeting ligands, the lipo‐polymersomes exhibit synergistically targeted gene delivery.