title: pH-responsive pHLIP (pH low insertion peptide) nanoclusters of superparamagnetic iron oxide nanoparticles as a tumor-selective MRI contrast agent.
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.
  
  
  
  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.
authors.affiliation: Department of Nanomedicine & Biopharmaceuticals, National Engineering Research Center for Nanomedicine, Huazhong University of Science and Technology, Wuhan 430074, China.
authors.forename: Yushuang
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Department of Radiology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
authors.forename: Rufang
authors.initials: R
authors.lastname: Liao
authors.affiliation: Department of Nanomedicine & Biopharmaceuticals, National Engineering Research Center for Nanomedicine, Huazhong University of Science and Technology, Wuhan 430074, China.
authors.forename: Abdulrahman Ahmed
authors.initials: AA
authors.lastname: Mahmood
authors.affiliation: Department of Radiology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China. Electronic address: xuhaibo1120@hotmail.com.
authors.forename: Haibo
authors.initials: H
authors.lastname: Xu
authors.affiliation: 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.
authors.forename: Qibing
authors.initials: Q
authors.lastname: Zhou
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000737:chemistry / Q000494:pharmacology; D016503:Drug Delivery Systems; D006801:Humans; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles / Q000737:chemistry / Q000627:therapeutic use; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry / Q000494:pharmacology; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology
chemical_list: D003287:Contrast Media; D058185:Magnetite Nanoparticles; D008565:Membrane Proteins; C533201:pHLIP protein
keywords: MRI imaging; SPION; Tumor selective imaging; pH low insertion peptide; pH-responsive