title: Upconversion nanoparticles conjugated with Gd(3+) -DOTA and RGD for targeted dual-modality imaging of brain tumor xenografts.
abstract: Glioblastoma multiforme (GBM) is the most common and malignant form of primary brain tumors in human. Small molecular magnetic resonance imaging (MRI) contrast agents are used for GBM diagnosis. However, conventional contrast agents have several limitations, such as low T1 relaxivity, short circulation half lives and absence of tumor targeting. Herein, we develop an upconversion nanoprobe labeled with Gd(3+) -DOTA and RGD (UCNP-Gd-RGD) for dual-modality imaging of glioblastoma. The preparation of UCNP-Gd-RGD starts with amine-functional upconversion nanoparticle core, followed by PEGylation, Gd(3+) DOTA conjugation and RGD labeling. The obtained UCNP-Gd-RGD has improved colloidal stability and reduced cytotoxicity compared with the UCNP core counterpart. Meanwhile, UCNP-Gd-RGD shows strong upconversion luminescence in deep-red region and three times enhancement of T1 relaxivity over Gd(3+) DOTA. Due to the recognition between UCNP-Gd-RGD and integrin αv β3 receptors, the nanoprobe specifically binds to U87MG cells, as evidenced by confocal microscopy and quantified by ICP-MS. Furthermore, UCNP-Gd-RGD demonstrates a preferential retention in subcutaneous U87MG tumor xenograft as shown in both in vivo upconversion fluorescence/MR imaging studies and ex vivo analysis. UCNP-Gd-RGD, conjugated with numerous RGD peptide and T1 contrast enhancing molecules, is promising for MR imaging of glioblastoma and delineating the tumor boundary before surgery. In addition, NIR-to-red upconversion characteristic of UCNP-Gd-RGD facilitates its potential intra-operative use for fluorescence-guided tumor resection.
authors: Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, P.R. China.
authors: Jiefu
authors: J
authors: Jin
authors: Zhenhua
authors: Z
authors: Xu
authors: Yue
authors: Y
authors: Zhang
authors: Yan-Juan
authors: YJ
authors: Gu
authors: Michael Hon-Wah
authors: MH
authors: Lam
authors: Wing-Tak
authors: WT
authors: Wong
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000175:diagnosis*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D004705:Endocytosis / Q000187:drug effects; D006571:Heterocyclic Compounds / Q000737:chemistry; D006801:Humans; D060328:Magnetic Phenomena; D008279:Magnetic Resonance Imaging; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D064847:Multimodal Imaging; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009842:Oligopeptides; D009942:Organometallic Compounds / Q000737:chemistry; D013054:Spectrophotometry, Atomic; D013499:Surface Properties; D023041:Xenograft Model Antitumor Assays
chemical_list: D006571:Heterocyclic Compounds; D009842:Oligopeptides; D009942:Organometallic Compounds; C047981:arginyl-glycyl-aspartic acid; C050823:gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate
keywords: dual-modality; fluorescence-guided surgery; glioblastoma; targeted imaging; upconversion