Functional Lanthanide-Based Nanoprobes for Biomedical Imaging Applications
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Functional Lanthanide-Based Nanoprobes for Biomedical Imaging Applications

Functional Lanthanide-Based Nanoprobes for Biomedical Imaging Applications


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About the Book

This dissertation, "Functional Lanthanide-based Nanoprobes for Biomedical Imaging Applications" by Jiefu, Jin, 金介夫, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Lanthanide-doped upconversion nanoparticles (UCNPs) are perceived as promising novel near-infrared (NIR) bioimaging agents characterised by high contrast and high penetration depth. However, the interactions between charged UCNPs and mammalian cells have not been thoroughly studied and the corresponding intracellular uptake pathways remain unclear. Herein, my research work involved the use of hydrothermal method and ligand exchange approach to prepare UCNP-PVP, UCNP-PEI, and UCNP-PAA. These polymer-coated UCNPs demonstrated good water dispersibility, the similar size distribution as well as similar upconversion luminescence efficiency. However, the positively charged UCNP-PEI evinced greatly enhanced cellular uptake in comparison with its neutral or negative counterparts, as revealed by cellular uptake studies. Meanwhile, it was discovered that cationic UCNP-PEI could be effectively internalized mainly through the clathrin endocytic machanism. This study is the first report on the endocytic mechanism of positively charged lanthanide-doped UCNPs. Furthermore, it allows us to control the UCNP-cell interactions by tuning surface properties. Glioblastoma multiforme (GBM) is the most common and malignant form of primary brain tumors in humans. Small molecule MRI contrast agents are used for GBM diagnosis and preoperative tumor margin delineation. However, the conventional gadolinium-based contrast agents have several disadvantages, such as a relatively low T1 relaxivity, short circulation half lives and the absence of tumor targeting efficiency. Multimodality imaging probes provide a better solution to clearly delineate the localization of glioblastoma. My research work also involved the development of multimodal nanoprobes for targeted glioblastoma imaging. Two targeted paramagnetic/fluorescence nanoprobes were designed and synthesized, UCNP-Gd-RGD and AuNP-Dy680-Gd-RGD. UCNP-Gd-RGD was prepared through PEGylation, Gd3+DOTA conjugation and RGD labeling of PEI-coated UCNP-based nanoprobe core (UCNP-NH2). It adopted the cubic NaYF4 phase, had an average size of 36 nm by TEM, and possessed a relatively intense upconversion luminescence of Er3+ and Tm3+. It also exhibited improved colloidal stability and reduced cytotoxicity compared with UCNP-NH2, and a higher T1 relaxivity than Gd3+DOTA. AuNP-Dy680-Gd-RGD was synthesized through bioconjugation of amine-modified AuNP-based nanoprobe core (AuNPPEG- NH2) by a NIR dye (Dy680), Gd3+DOTA and RGD peptide. It demonstrated a size of 3-6 nm by TEM, relatively strong NIR fluorescence centered at 708 nm, longterm physiological stability, and an enhanced T1 relaxivity compared with Gd3+DOTA. Targeting abilities of both UCNP-Gd-RGD and AuNP-Dy680-Gd-RGD towards overexpressed integrin αvβ3 receptors on U87MG cell surface was confirmed by their enhanced cellular uptake visualized by confocal microscopy imaging and quantified by ICP-MS, where their corresponding control nanoprobes were used for comparison. Furthermore, targeted imaging capabilities of UCNP-Gd-RGD and AuNP-Dy680-Gd- RGD towards subcutaneous U87MG tumors were verified by in viv


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Product Details
  • ISBN-13: 9781361306352
  • Publisher: Open Dissertation Press
  • Publisher Imprint: Open Dissertation Press
  • Height: 279 mm
  • No of Pages: 216
  • Weight: 513 gr
  • ISBN-10: 1361306351
  • Publisher Date: 26 Jan 2017
  • Binding: Paperback
  • Language: English
  • Spine Width: 12 mm
  • Width: 216 mm


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