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  • br a State Key Laboratory of Fine

    2019-10-07


    a State Key Laboratory of Fine Chemicals, School of Chemistry, Dalian University of Technology, Dalian 116024, China
    b Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St. Lucia, QLD 4072, Australia
    c Department of Pathophysiology, Dalian Medical University, Dalian 116044, China
    Keywords:
    Cancer cells
    Dual-emissive nanoprobe
    Luminescence imaging
    Time-gated luminescence imaging
    Folic acid 
    Development of luminescent probes for rapid and effective discrimination and detection of cancer cells has the potential to address the current challenges in early diagnosis and treatment monitoring of cancer diseases. In this work, we report the preparation of a unique folic Paxilline (FA)-functionalized dual-emissive nanoprobe, [email protected] BHHBCB-Eu-FA, for steady-state and time-gated luminescence “double-check” imaging of cancer cells. The nanoprobe Paxilline was engineered by covalently doping two luminescent dyes, 5-carboxytetramethylrhodamine (CTMR) and BHHBCB-Eu3+, in core and shell of silica nanoparticles, followed by surface modification of the nanoparticles with FA, a cancer cell-targeting molecule. As-prepared nanoprobe is monodisperse and highly stable in buffer displaying two strong emissions, short-lived emission from CTMR at 584 nm and long-lived emission from BHHBCB-Eu3+ at 612 nm. The nanoprobe is biocompatible, and can specifically recognize folate receptor (FR)-overexpressed cancer cells through the FA-FR binding interaction. Using the nanoprobe, the “double-check” imaging of HeLa cells was successfully achieved at steady-state and time-gated luminescence modes, indicating the capability of the nanoprobe for cancer cell imaging.
    1. Introduction
    Cancers have been identified as the leading human disease of death worldwide, causing more than 9.6 million deaths globally in 2018 [1]. Abnormal growth and further cancerization of cells are typically in-volved in the progression of cancer diseases [2,3]. Therefore, the de-tection of cancer cells is emerging to be a potentially valuable approach for real-time monitoring of cancer progression and further investigation of cancer biology at the cell level [4,5]. From a point view of clinical diagnosis and treatment of cancers, it is especially important to develop specific probes for identification and detection of cancer cells in com-plicated biological conditions [6–8]. To develop such a probe generally requires the integration of a suitable signalling unit with a biomolecule that can specifically recognize cancer cells [9–12]. Using these probes, it becomes possible to detect cancer cells in biological fluids as well as to visualize these cells in vitro and in vivo, thus potentially contributing to the early diagnosis and treatment monitoring of cancer diseases.
    To date, a variety of probes [13–22], namely the contrast agents, have been developed for the imaging of cancers by virtue of computer tomography (CT), magnetic resonance imaging (MRI), single-photon
    emission computed tomography (SPECT), positron emission tomo-graphy (PET), and luminescent imaging technologies. Of these methods, luminescent imaging using fluorescent/phosphorescent probes has shown attractive advantages in detection of cancer cells due to its high sensitivity and selectivity, low cost, and experimental sim-plicity [9,23–27]. In addition, with the advance of luminescence mi-croscopy technique, tracking of a signal cancer cell has been readily achieved with highly spatial and temporal resolutions [28–32]. Nevertheless, the majority of luminescent detection and imaging of cancer cells using conventional probes relies on a single emission signal, which may be interfered by the strong autofluorescence from biological tissues, to give false positive results [33,34].