title: A Prodrug-type, MMP-2-targeting Nanoprobe for Tumor Detection and Imaging.
abstract: Tumor-associated proteases (TAPs) have been intensively studied because of their critical roles in cancer development. As a case in point, expression of matrix metalloproteases (MMP) is significantly up-regulated in tumorigenesis, invasion, and metastasis among a majority of cancers. Here we present a prodrug-type, MMP-2-responsive nanoprobe system with high efficiency and low toxicity for detecting MMP-2-overexpressed tumors. The nanoprobe system is featured by its self-assembled fabrication and FRET effect. This prodrug-type nanoprobe is selectively activated by MMP-2, and thus useful for detection of the MMP-2-overexpressed cells and tumors. The nanoprobe system works successfully in various animal tumor models, including human fibrosarcoma and subcutaneous glioma xenograft. Furthermore, in order to overcome the blood brain barrier (BBB) and achieve brain tumor targeting, a transferrin-receptor targeting peptide (T7 peptide) is strategically incorporated into the nanoprobe. The T7-functionalized nanoprobe is capable of detecting the orthotopic brain tumor, with clear, real-time in vivo imaging. This method is promising for in vivo detection of brain tumor, and real-time monitor of a TAP (i.e., MMP-2).
authors.affiliation: 1. Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin 300070, China. ; 2. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Hai-ke Rd, Shanghai 201203, China.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Wang
authors.affiliation: 1. Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin 300070, China. ; 2. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Hai-ke Rd, Shanghai 201203, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Lin
authors.affiliation: 2. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Hai-ke Rd, Shanghai 201203, China.
authors.forename: Wenyuan
authors.initials: W
authors.lastname: Zhang
authors.affiliation: 2. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Hai-ke Rd, Shanghai 201203, China.
authors.forename: Yifan
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: 2. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Hai-ke Rd, Shanghai 201203, China.
authors.forename: Hongyue
authors.initials: H
authors.lastname: Jin
authors.affiliation: 1. Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Huining
authors.initials: H
authors.lastname: He
authors.affiliation: 1. Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin 300070, China. ; 3. University of Michigan, College of Pharmacy, 428 Church St, Ann Arbor, MI 48108, USA.
authors.forename: Victor C
authors.initials: VC
authors.lastname: Yang
authors.affiliation: 2. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Hai-ke Rd, Shanghai 201203, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Chen
authors.affiliation: 2. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Hai-ke Rd, Shanghai 201203, China.
authors.forename: Yongzhuo
authors.initials: Y
authors.lastname: Huang
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000473:pathology; D004195:Disease Models, Animal; D005354:Fibrosarcoma / Q000175:diagnosis / Q000473:pathology; D005910:Glioma / Q000175:diagnosis / Q000473:pathology; D064593:Heterografts; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000032:analysis*; D008807:Mice, Inbred BALB C; D049329:Nanostructures / Q000008:administration & dosage*; D061848:Optical Imaging / Q000379:methods*; D011355:Prodrugs / Q000493:pharmacokinetics*; D000068936:Theranostic Nanomedicine / Q000379:methods*
chemical_list: D011355:Prodrugs; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2
keywords: brain tumor; fluorescence resonance energy transfer.; matrix metalloprotease; protease-activatable probe; tumor imaging