Targeting N-acetylglucosamine-bearing polymer-coated liposomes to vascular smooth muscle cells
The targeted delivery of anti-inflammatory agents has great therapeutic potential for treating restenosis following percutaneous coronary intervention. To develop a drug delivery system targeted to injured blood vessels, we examined whether N-acetylglucosamine (GlcNAc)-bearing polymer-coated liposomes (GlcNAc-Ls) are specifically taken up by vascular smooth muscle cells (VSMCs). Flow cytometric analysis revealed that GlcNAc-Ls were taken up by VSMCs in vitro. Furthermore, GlcNAc-Ls were intravenously administered to mice that had undergone wire-mediated vascular injury. GlcNAc-Ls markedly accumulated at the intramural site of the injured vessel walls but not at the contralateral (uninjured) vessel walls. These results demonstrated that GlcNAc-Ls can be specifically taken up by VSMCs both in vitro and in vivo. We propose a novel strategy of using GlcNAc-Ls that has potential for application in drug delivery targeted to injured blood vessels.
KeywordsDrug delivery system N-acetylglucosamine Lectin Restenosis Vascular smooth muscle cells
This work was supported in part by a Grant-in-Aid for Scientific Research on Innovative Areas (No. 20200016) from the Ministry of Education, Science, Sports, Culture, and Technology of Japan. We are grateful to Dr. Nakagami from Osaka University for providing NF-κB decoy oligonucleotides.
- 13.Yamasaki K, Asai T, Shimizu M, Aoki M, Hashiya N, Sakonjo H, Makino H, Kaneda Y, Ogihara T, Morishita R. Inhibition of NF-kappaB activation using cis-element ‘decoy’ of NF-kappaB binding site reduces neointimal formation in porcine balloon-injured coronary artery model. Gene Ther. 2003;10:356–64.PubMedCrossRefGoogle Scholar
- 16.Sata M, Maejima Y, Adachi F, Fukino K, Saiura A, Sugiura S, Aoyagi T, Imai Y, Kurihara H, Kimura K, Omata M, Makuuchi M, Hirata Y, Nagai R. A mouse model of vascular injury that induces rapid onset of medial cell apoptosis followed by reproducible neointimal hyperplasia. J Mol Cell Cardiol. 2000;32:2097–104.PubMedCrossRefGoogle Scholar
- 19.Morimoto H, Takahashi M, Shiba Y, Izawa A, Ise H, Hongo M, Hatake K, Motoyoshi K, Ikeda U. Bone marrow-derived CXCR4+ cells mobilized by macrophage colony-stimulating factor participate in the reduction of infarct area and improvement of cardiac remodeling after myocardial infarction in mice. Am J Pathol. 2007;171:755–66.PubMedCrossRefGoogle Scholar