NDLI: Anti-angiogenic nanotherapy <i>via</i> active targeting systems to tumors and adipose tissue vasculature

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Anti-angiogenic nanotherapy via active targeting systems to tumors and adipose tissue vasculature

Content Provider	Royal Society of Chemistry (RSC)
Author	Sakurai, Yu Harashima, Hideyoshi Kajimoto, Kazuaki
Copyright Year	2015
Abstract	Sophisticated drug delivery systems (DDS) are required for delivering drugs, especially macromolecules such as nucleic acids or proteins, to their sites of action. Therefore it is a prerequisite that future DDS are designed to selectively target a tissue. In this review, we focus on systems that actively target the vasculature in tumors or adipose tissues. For targeting tumor vasculatur, a new strategy referred to as dual-targeting is proposed that uses a combination of a receptor specific ligand and a cell penetrating peptide, which can induce the synergistic enhancement of tissue selectivity under in vivo conditions. A novel pH-sensitive cationic lipid was designed to enhance the endosomal release of encapsulated compounds such as siRNA as well as to improve the stability in blood circulation after intravenous administration. A cyclic RGD peptide is used as an active targeting ligand. For targeting adipose vasculature, prohibitin, which is expressed on the surface of adipose endothelial cells, was targeted with KGGRAKD peptides on the surface of PEGylated nanoparticles. Prohibitin targeted nanoparticles (PTNP) encapsulating Cytochrome c (CytC) can selectively target adipose vasculature by optimizing the lengths of the PEG linkers and can deliver CytC to adipose endothelial cells. PTNP can successfully induce anti-obese effects as well as apoptosis by delivering CytC to the cytosol in endothelial cells. Unexpectedly, the EPR (enhanced permeability and retention) effect, which is usually observed in tumor tissue, was also observed in the adipose vasculature, especially in obese mice, where PEGylated nanoparticles can pass through the endothelial barriers in adipose tissue. We believe that these achievements in active targeting will allow a greatly expanded use of DDS for nanomedicines.
Starting Page	1253
Ending Page	1265
Page Count	13
File Format	HTM / HTML PDF
ISSN	20474830
Volume Number	3
Issue Number	9
Journal	Biomaterials Science
DOI	10.1039/c5bm00113g
Language	English
Publisher	Royal Society of Chemistry
Access Restriction	Open
Subject Keyword	Adipocyte Adipose tissue Cell membrane Cell surface receptor Ligand EPR Small interfering RNA Drug delivery Cytosol Lipid Endothelium Peptide Prohibitin Cell-penetrating peptide Apoptosis
Content Type	Text
Resource Type	Article
Subject	Materials Science Biomedical Engineering

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