Upconversion nanoparticles conjugated with Gd3+-DOTA and RGD for targeted dual-modality imaging of brain tumor xenografts

Jiefu Jin, Zhenhua Xu, Yue Zhang, Yan Juan Gu, Michael Hon Wah Lam, Wing Tak Wong

Research output: Journal article publicationJournal articleAcademic researchpeer-review

62 Citations (Scopus)

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 Gd3+-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, Gd3+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 Gd3+DOTA. Due to the recognition between UCNP-Gd-RGD and integrin αvβ3 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. KGaA, Weinheim.
Original languageEnglish
Pages (from-to)1501-1512
Number of pages12
JournalAdvanced healthcare materials
Volume2
Issue number11
DOIs
Publication statusPublished - 1 Nov 2013

Keywords

  • Dual-modality
  • Fluorescence-guided surgery
  • Glioblastoma
  • Targeted imaging
  • Upconversion

ASJC Scopus subject areas

  • Biomedical Engineering
  • Biomaterials
  • Pharmaceutical Science

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