2. Academic Validation
  3. pH-responsive pHLIP (pH low insertion peptide) nanoclusters of superparamagnetic iron oxide nanoparticles as a tumor-selective MRI contrast agent

pH-responsive pHLIP (pH low insertion peptide) nanoclusters of superparamagnetic iron oxide nanoparticles as a tumor-selective MRI contrast agent

  • Acta Biomater. 2017 Jun;55:194-203. doi: 10.1016/j.actbio.2017.03.046.
Yushuang Wei 1,  Rufang Liao 2,  Abdulrahman Ahmed Mahmood 1,  Haibo Xu 3,  Qibing Zhou 4
Affiliations

Affiliations

  • 1 Department of Nanomedicine & Biopharmaceuticals, National Engineering Research Center for Nanomedicine, Huazhong University of Science and Technology, Wuhan 430074, China.
  • 2 Department of Radiology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
  • 3 Department of Radiology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China. Electronic address: xuhaibo1120@hotmail.com.
  • 4 Department of Nanomedicine & Biopharmaceuticals, National Engineering Research Center for Nanomedicine, Huazhong University of Science and Technology, Wuhan 430074, China. Electronic address: qibingzhou@hust.edu.cn.
PMID: 28363789 DOI: 10.1016/j.actbio.2017.03.046
Abstract

Superparamagnetic iron oxide nanoparticles (SPION) are contrast agents used for noninvasive tumor magnetic resonance imaging (MRI). SPION with active targeting by tumor-specific ligands can effectively enhance the MRI sensitivity and specificity of tumors. However, the challenge remains when the tumor specific markers are yet to be determined, especially in the case of early tumor detection. In this study, the effectiveness of pH-responsive SPION via a pH low insertion peptide (pHLIP) to target tumor acidic microenvironments was investigated. Polylysine Polymers were first successfully modified with pHLIP to have the pH-responsive capability. SPION pHLIP nanoclusters of 64, 82, 103, and 121nm size were then assembled by the pH-responsive Polymers in a size-controlled manner. The pH-responsive SPION nanoclusters of the 64nm size exhibited the most effective pH-responsive retention in cells and tumor selective imaging in MRI. More importantly, the unique contrast enhancement of tumor inner core by the pH-responsive SPION in three different tumor models demonstrated the clinical potential to target tumor acidic microenvironment through pHLIP for tumor early detection and diagnosis by MRI.

Statement of significance: Detection and diagnosis of tumors at early stage are critical for the improvement of the survival rate of Cancer patients. However, the challenge remains when the tumor specific markers are yet to be determined, especially in early tumor detection. pH low insertion peptide (pHLIP) has been used as a specific ligand to target the tumor acidic microenvironment for tumors at early and metastatic stages. Superparamagnetic iron nanoparticles (SPION) are contrast enhancing agents used in the noninvasive magnetic resonance imaging for tumors. This research has demonstrated that pH-responsive pHLIP nanoclusters of SPION were able to target different tumors and facilitate the noninvasive diagnosis of tumors by MRI.

Keywords

MRI imaging; SPION; Tumor selective imaging; pH low insertion peptide; pH-responsive.

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