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A neutral lipid envelope-type nanoparticle composed of a pH-activated and vitamin E-scaffold lipid-like material as a platform for a gene carrier targeting renal cell carcinoma

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Please use this identifier to cite or link to this item:http://hdl.handle.net/2115/58129

Title: A neutral lipid envelope-type nanoparticle composed of a pH-activated and vitamin E-scaffold lipid-like material as a platform for a gene carrier targeting renal cell carcinoma
Authors: Akita, Hidetaka Browse this author →KAKEN DB
Ishiba, Ryohei Browse this author
Togashi, Ryohei Browse this author
Tange, Kota Browse this author
Nakai, Yuta Browse this author
Hatakeyama, Hiroto Browse this author →KAKEN DB
Harashima, Hideyoshi Browse this author →KAKEN DB
Keywords: Cancer
Gene delivery
Renal carcinoma
Angiogenesis
Issue Date: 28-Feb-2015
Publisher: Elsevier
Journal Title: Journal of controlled release
Volume: 200
Start Page: 97
End Page: 105
Publisher DOI: 10.1016/j.jconrel.2014.12.029
PMID: 25543000
Abstract: A renal cell carcinoma (RCC) is one of the refractory tumors, since it readily acquires resistance against chemotherapy. Thus, alternative therapeutic approaches such as obstructing the neovasculature are needed. We previously reported on the development of a plasmid DNA (pDNA)-encapsulating liposomal nanoparticle (LNP) as a hepatic gene delivery system that is applicable to systemic administration. The key molecular component is a SS-cleavable and pH-activated lipid-like material (ssPalm) that mounts dual sensing motifs (ternary amines and disulfide bonding) that are responsive to the intracellular environment. The main purpose of the present study was to expand its application to a tumor-targeting gene delivery systemin mice bearing tumors established from a RCC (OS-RC-2). When the modification of the surface of the particle is optimized for the polyethyleneglycol (PEG), stability in the blood circulation is improved, and consequently tumor-selective gene expression can be achieved. Furthermore, gene expression in the tumor was increased slightly when the hydrophobic scaffold of the ssPalm was replaced from the conventionally used myristic acid (ssPalmM) to alpha-tocopherol succinate (ssPalmE). Moreover, tumor growth was significantly suppressed when the completely CpG-free pDNA encoding the solute form of VEGFR (fms-like tyrosine kinase-1: sFlt-1) was used, especially when it was delivered by the LNP formed with ssPalmE(LNPssPalmE). Thus, the PEG-modified LNPssPalmE is a promising gene carrier for the cancer gene therapy of RCC. (C) 2014 Elsevier B.V. All rights reserved.
Type: article (author version)
URI: http://hdl.handle.net/2115/58129
Appears in Collections:薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 秋田 英万

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