Multi-nanoDDS platform based on the intracellular environment-responsive material  (ssPalm) : Delivery of gene/nucleic acid delivery

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Abstract

Development of the nanotechnologies to control an intracellular trafficking, and release of the cargos are required to open a new-generation of therapeutics using genes or nucleic acids. Quantitative analysis of the intracellular trafficking of lipoplex with adenovirus revealed that the poor post-nuclear delivery events, as well as nuclear delivery process (i.e. transcription and translation) are key processes to be overcome in the conventional cationic carriers. Especially, less effective transcription and translation is most likely due to the poor nuclear decondensation and association between mRNA and cationic carrier, respectively via electrostatic interaction. Also, when the cationic particle was administered intravenously, they formed large aggregates, and then stacked in the lung capillary. Also, in vivo gene expression was peaked at 6 h after the transfection, and then rapidly decreased within 2 days. To overcome these drawback, we recently developed a SS-cleavable and pH-activated lipid-like material (ssPalm) to prepare a neutral nanoparticle, that can be charged positive in acidic environment in endosome, and be collapsed in response to the reductive environment in cytoplasm. Since the vitamins have unique physicochemical properties, transport system and physiological function, we employed vitamin A and vitamin E as a hydrophobic scaffold to functionalize the ssPalm particle. When the particle was taken up by endocytosis, the vesicles were transferred to the lysosomal degradation pathway. In this process, endosomal pH gradually decreased. Thus, we design a particle that can detect a slight change of endosomal acidification, and then charged positive for the rapid endosomal escape at earlier stage. Based on this concept, we modified the amine structure so as to allow it to receive protons readily. The particle is a novel nanoDDS platform that can deliver genes, nucleic acids and low-molecular compounds. In this manuscript, we focused on the application of the ssPalm particle as a carrier of DNA and siRNA.

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Tanaka, H., & Akita, H. (2016). Multi-nanoDDS platform based on the intracellular environment-responsive material  (ssPalm) : Delivery of gene/nucleic acid delivery. Drug Delivery System, 31(1), 24–34. https://doi.org/10.2745/dds.31.24

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