Facile Preparation of Well-Defined Hydrophilic Core鈥揝hell Upconversion Nanoparticles for Selective Cell Membrane Glycan Labeling and Cancer Cell Imaging
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文摘
Molecular imaging enables in situ visualization of biomolecules in living organisms and creates numerous opportunities for basic biological research and early disease diagnosis. As luminescent probes for molecular imaging, lanthanide-doped upconversion nanoparticles (UCNPs) exhibit superior performance compared to conventional fluorescent dyes in many ways, including high tissue penetration depth and minimized autofluorescence and photobleaching, making them particularly advantageous for imaging analysis. Although various synthesis methods have been reported, the preparation of high quality, water-soluble UCNPs remains challenging. For in situ imaging, glycans on the cell surface are particularly attractive due to their key roles in cellular activity and disease occurrence and development. However, glycan imaging is a challenging task due to their diverse structures and incompatibility with genetically encoded fluorescent tagging techniques. Herein, we report a new type of highly water-soluble, lectin-functionalized core鈥搒hell UCNP synthesized by surface-initiated atom transfer radical polymerization (SI-ATRP) for selective cell membrane glycan labeling and cancer cell imaging. SI-ATRP modification results in controlled growth of hydrophilic polymers on the UCNP surface and well-defined core鈥搒hell structure, producing UCNPs with improved biocompatibility and intact luminance property. Furthermore, the numerous functional groups on the polymer brush shell provide a large number of binding sites and 3D support for lectin immobilization. The increased loading density and diversified architecture of the immobilized lectins facilitates multivalent binding between the lectins and the glycans on the cell surface and leads to selective labeling of highly metastatic hepatocellular carcinoma cells (HCCHM3) in vitro and successful in vivo imaging of HCCHM3 inoculated mice.

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