4.5 Article

A Dual-Ligand Liposomal System Composed of a Cell-Penetrating Peptide and a Mitochondrial RNA Aptamer Synergistically Facilitates Cellular Uptake and Mitochondrial Targeting

期刊

JOURNAL OF PHARMACEUTICAL SCIENCES
卷 105, 期 5, 页码 1705-1713

出版社

WILEY
DOI: 10.1016/j.xphs.2016.03.002

关键词

targeted drug delivery; liposomes; aptamer; drug delivery systems; nanotechnology

资金

  1. Ministry of Education, Culture, Sports, Science, and Technology [26282131]
  2. Japanese Government (MEXT)
  3. Mochida Memorial Foundation for Medical and Pharmaceutical Research
  4. Uehara Memorial Foundation

向作者/读者索取更多资源

It has been reported that the use of mitochondrial RNA aptamers including RNase P (RP) results in the selective mitochondrial delivery of endogenous and exogenous RNAs. The issue of whether these aptamers would be useful ligands for the mitochondrial targeting of a nanoparticle has not been demonstrated to date because nanocarriers modified with these RNA aptamers are insufficiently internalized by cells. We report here on the development of a dual-ligand liposomal system composed of octaarginine (R8), a device that enhances cellular uptake, and an RP aptamer for mitochondrial targeting to permit a nanocarrier to be efficiently delivered to mitochondria. Surprisingly, the cellular uptake of the R8-modified nanocarrier was facilitated by modification with an RP aptamer. The optimal composition of a nanocarrier needed for efficient cellular uptake and mitochondrial targeting was determined. In a confocal laser scanning microscopy analysis, the dual-ligandemodified nanocarrier was found to result in effective mitochondrial targeting through an ATP-dependent pathway and was much more effective than a single-ligand R8-modified nanocarrier. This is the first report of the regulation of intracellular trafficking by a mitochondrial RNA aptamer-modified nanocarrier system. (C) 2016 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.

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