Journal
JOURNAL OF CONTROLLED RELEASE
Volume 193, Issue -, Pages 316-323Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2014.04.023
Keywords
Gene therapy; Drug delivery system; MEND; pDNA; siRNA; Active targeting
Funding
- Special Education and Research Expenses of the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT)
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We report on the development of a multifunctional envelope-type nano device (MEND) based on our packaging concept Programmed packaging to control not only intracellular trafficking but also the biodistribution of encapsulated compounds such as nucleic acids/proteins/peptides. Our strategy for achieving this is based on molecular mechanisms of cell biology such as endocytosis, vesicular trafficking, etc. In this review, we summarize the concept of programmed packaging and discuss some of our recent successful examples of using MENDs. Systematic evolution of ligands by exponential enrichment (SELEX) was applied as a new methodology for identifying a new ligand toward cell or mitochondria. The delivery of siRNA to tumors and the tumor vasculature was achieved using pH sensitive lipid (YSK05), which was newly designed and optimized under in vivo conditions. The efficient delivery of pDNA to immune cells such as dendritic cells has also been developed using the KALA ligand, which can be a breakthrough technology for DNA vaccine. Finally, ss-cleavable and pH-activated lipid-like surfactant (ssPalm) which is a lipid like material with pH-activatable and SS-cleavable properties is also introduced as a proof of our concept. (C) 2014 Elsevier B.V. All rights reserved.
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