Format

Send to

Choose Destination
Biomaterials. 2019 Sep;214:119224. doi: 10.1016/j.biomaterials.2019.119224. Epub 2019 May 23.

Multi-layer surface modification of pancreatic islets for magnetic resonance imaging using ferumoxytol.

Author information

1
Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
2
Stem Cell & Regenerative Medicine Institute, Samsung Medical Center, Seoul, Republic of Korea; Medical Research Institute, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
3
Research Institute of Pharmaceutical Science, College of Pharmacy, Seoul National University, Seoul, Republic of Korea.
4
Animal Research and Molecular Imaging Center, Samsung Medical Center, Seoul, Republic of Korea.
5
Stem Cell & Regenerative Medicine Institute, Samsung Medical Center, Seoul, Republic of Korea.
6
Stem Cell & Regenerative Medicine Institute, Samsung Medical Center, Seoul, Republic of Korea; New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation (DGMIF), Daegu, Republic of Korea.
7
Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, Republic of Korea.
8
Department of Bioengineering, College of Engineering, and BK21 PLUS Team, and Institute of Nano Science & Technology (INST), Hanyang University, Seoul, 04763, Republic of Korea.
9
Research Institute of Pharmaceutical Science, College of Pharmacy, Seoul National University, Seoul, Republic of Korea. Electronic address: yrbyun@snu.ac.kr.
10
Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; Stem Cell & Regenerative Medicine Institute, Samsung Medical Center, Seoul, Republic of Korea; Department of Health Science and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea. Electronic address: jaehyeon@skku.edu.

Abstract

Ferumoxytol is the only clinically available ultrasmall superparamagnetic iron oxide. However, the labeling efficacy of islet magnetic resonance imaging (MRI) using ferumoxytol is not suitable for use in clinical pancreatic islet transplantation (PIT). We evaluated the feasibility of pancreatic islet MRI using ferumoxytol through multi-layer surface modification. A four-layer nanoshield with poly (ethylene) glycol (PEG, 2 layers), ferumoxytol, and heparin was formed on the pancreatic islets. We compared pancreatic islet function, viability, and labeling efficacy of control, ferumoxytol alone-labeled, heparin-PEGylated, and ferumoxytol-heparin-PEGylated islets. With optimization of the ferumoxytol concentration during the ferumoxytol-heparin-PEGylation process, the labeling contrast in ex vivo MRI of ferumoxytol-heparin-PEGylated pancreatic islets was stronger than that of pancreatic islets labeled with ferumoxytol alone, without decreasing ex vivo islet viability or function. In a syngeneic mouse renal subcapsular PIT model, heparin-PEGylation and ferumoxytol-heparin-PEGylation delayed the revascularization of pancreatic islet grafts but did not impair glucose tolerance or revascularization of pancreatic islet grafts four weeks post-transplantation. Pancreatic islet visibility after labeling was also confirmed in a syngeneic mouse intraportal PIT model and in preliminary analysis of a non-human primate intraportal PIT model. In conclusion, multi-layer islet surface modification is a promising option for pancreatic islet MRI in intraportal PIT.

KEYWORDS:

Islet; Magnetic resonance imaging; Nanoparticle; PEGylation; Transplantation

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center