Scavenger Receptor A-Mediated Targeting of Carboxylated Polyrotaxanes to Macrophages and the Impacts of Supramolecular Structure

Hideto Matsui; Atsushi Tamura; Mamoru Osawa; Asato Tonegawa; Yoshinori Arisaka; Mitsuaki Matsumura; Hiroyuki Miura; Nobuhiko Yui

doi:10.1002/mabi.201800059

Scavenger Receptor A-Mediated Targeting of Carboxylated Polyrotaxanes to Macrophages and the Impacts of Supramolecular Structure

Macromol Biosci. 2018 Aug;18(8):e1800059. doi: 10.1002/mabi.201800059. Epub 2018 Jun 13.

Authors

Hideto Matsui¹, Atsushi Tamura², Mamoru Osawa², Asato Tonegawa², Yoshinori Arisaka², Mitsuaki Matsumura¹, Hiroyuki Miura¹, Nobuhiko Yui²

Affiliations

¹ Department of Restorative Sciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo, Tokyo, 113-8549, Japan.
² Department of Organic Biomaterials, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University (TMDU), 2-3-10 Kanda-Surugadai, Chiyoda, Tokyo, 101-0062, Japan.

PMID: 29900668
DOI: 10.1002/mabi.201800059

Abstract

Because macrophages are involved in the pathology of many diseases, targeting delivery of therapeutic molecules to macrophages is important issue. Polyrotaxanes (PRXs) composed of multiple cyclodextrins threaded with a linear polymer were utilized as a therapeutic agent for metabolic disease and for regulating cellular metabolism. For targeting delivery of PRXs to macrophages, carboxyethyl ether group-modified PRXs (CEE-PRXs) are designed for promoting interaction to macrophage scavenger receptor class A (SR-A). The cellular internalization of anionic CEE-PRXs in SR-A-positive macrophage-like cells (RAW264.7) is remarkably higher than that of nonionic PRX, whereas the cellular internalization efficiency in SR-A-negative cells is comparable between anionic and nonionic PRX. Furthermore, the molecular weight of axle polymer and the number of CEE groups modified on PRX are found to be the predominant factors governing cellular internalization efficiency in SR-A-positive RAW264.7 cells. Thus, CEE-PRXs are a promising design for targeting delivery of PRXs to macrophages.

Keywords: carboxy group; cyclodextrin; macrophage; polyrotaxane; scavenger receptor.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Drug Carriers*
Macrophages / drug effects*
Macrophages / metabolism
Mice
RAW 264.7 Cells
Rotaxanes / administration & dosage*
Scavenger Receptors, Class A*

Substances

Drug Carriers
Rotaxanes
Scavenger Receptors, Class A