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Upconversion Nanoparticles Conjugated with Gd 3+ ‐DOTA and RGD for Targeted Dual‐Modality Imaging of Brain Tumor Xenografts
Author(s) -
Jin Jiefu,
Xu Zhenhua,
Zhang Yue,
Gu YanJuan,
Lam Michael HonWah,
Wong WingTak
Publication year - 2013
Publication title -
advanced healthcare materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.288
H-Index - 90
eISSN - 2192-2659
pISSN - 2192-2640
DOI - 10.1002/adhm.201300102
Subject(s) - nanoprobe , in vivo , conjugated system , magnetic resonance imaging , dota , photon upconversion , cancer research , fluorescence lifetime imaging microscopy , biophysics , fluorescence , chemistry , materials science , medicine , nanoparticle , nanotechnology , biology , radiology , polymer , ion , physics , microbiology and biotechnology , organic chemistry , quantum mechanics
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 T 1 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 T 1 relaxivity over Gd 3+ DOTA. Due to the recognition between UCNP‐Gd‐RGD and integrin α v β 3 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 T 1 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.