Evaluation of non-targeting, C- or N-pH (low) insertion peptide modified superparamagnetic iron oxide nanoclusters for selective MRI of liver tumors and their potential toxicity in cirrhosis

Abdulrahman Ahmed Mahmood; Jianqi Zhang; Rufang Liao; Xiwei Pan; Dan Xu; Haibo Xu; Qibing Zhou

doi:10.1039/c9ra02430a

Evaluation of non-targeting, C- or N-pH (low) insertion peptide modified superparamagnetic iron oxide nanoclusters for selective MRI of liver tumors and their potential toxicity in cirrhosis

RSC Adv. 2019 May 7;9(25):14051-14059. doi: 10.1039/c9ra02430a.

Authors

Abdulrahman Ahmed Mahmood¹, Jianqi Zhang¹, Rufang Liao², Xiwei Pan¹, Dan Xu², Haibo Xu², Qibing Zhou¹

Affiliations

¹ Department of Nanomedicine & Biopharmaceuticals, College of Life Science and Technology, National Engineering Research Center for Nanomedicine, Huazhong University of Science and Technology Wuhan 430074 Hubei China qibingzhou@hust.edu.cn.
² Department of Radiology, Zhongnan Hospital of Wuhan University Wuhan 430071 Hubei China xuhaibo1120@hotmail.com.

Abstract

Superparamagnetic iron oxide nanoclusters (SPIONs) modified with pH (low) insertion peptide (pHLIP) could be advantageous for magnetic resonance imaging (MRI) diagnosis of liver tumors at the early stage due to their unique responsiveness to the tumor acidic microenvironment when tumor markers are unknown. However, many critical aspects including the effectiveness of selective MRI in liver tumors, types of delivery and the potential safety profile in cirrhosis need to be fully evaluated. In this study, we report the evaluation of non-targeting, C- or N-pHLIP modified SPIONs as the contrast agent for selective MRI of liver tumors and their potential toxicity profile in cirrhosis. It was found that N-pHLIP modified SPIONs did not result in the loss of liver tumor in the T2-weight MRI but provided additional dynamic details of tumor structures that would enhance the diagnosis of liver tumors at a small size below 8 mm. In addition, an enhanced safety profile was found for N-pHLIP modified SPIONs with almost fully recoverable impact in cirrhosis. In contrast, the poly-d-lysine assembled SPIONs and C-terminus linked pHLIP SPIONs had non-tumor specific MRI contrast enhancement and potential safety risks in cirrhosis due to the iron overload post injection. All these results implied the promising potential of N-terminus linked pHLIP SPIONs as an MRI contrast agent for the diagnosis of liver tumors.