title: Polymer-coated NaYF₄:Yb³⁺, Er³⁺ upconversion nanoparticles for charge-dependent cellular imaging.
abstract: Lanthanide-doped upconversion nanoparticles (UCNPs) are considered promising novel near-infrared (NIR) bioimaging agents with the characteristics of 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, our research work involved the use of a hydrothermal method to synthesize polyvinylpyrrolidone-coated UCNPs (UCNP-PVP), and then a ligand exchange reaction was performed on UCNP-PVP, with the help of polyethylenimine (PEI) and poly(acrylic acid) (PAA), to generate UCNP-PEI and UCNP-PAA. These polymer-coated UCNPs demonstrated good dispersibility in aqueous medium, had the same elemental composition and crystal phase, shared similar TEM and dynamic light scattering (DLS) size distribution, and exhibited similar upconversion luminescence efficiency. However, the positively charged UCNP-PEI evinced greatly enhanced cellular uptake in comparison with its neutral or negative counterparts, as shown by multiphoton confocal microscopy and inductively coupled plasma mass spectrometry (ICP-MS) measurements. Meanwhile, we found that cationic UCNP-PEI can be effectively internalized mainly through the clathrin endocytic mechanism, as revealed by colocalization, chemical, and genetic inhibitor studies. This study elucidates the role of the surface polymer coatings in governing UCNP-cell interactions, and it is the first report on the endocytic mechanism of positively charged lanthanide-doped UCNPs. Furthermore, this study provides important guidance for the development of UCNPs as specific intracellular nanoprobes, allowing us to control the UCNP-cell interactions by tuning surface properties.
authors: Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong.
authors: Jiefu
authors: J
authors: Jin
authors: Yan-Juan
authors: YJ
authors: Gu
authors: Cornelia Wing-Yin
authors: CW
authors: Man
authors: Jinping
authors: J
authors: Cheng
authors: Zhenhua
authors: Z
authors: Xu
authors: Yue
authors: Y
authors: Zhang
authors: Huaishan
authors: H
authors: Wang
authors: Vien Hoi-Yi
authors: VH
authors: Lee
authors: Shuk Han
authors: SH
authors: Cheng
authors: Wing-Tak
authors: WT
authors: Wong
mesh_terms: D002746:Chlorpromazine / Q000494:pharmacology; D002966:Clathrin / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics; D018699:Coated Vesicles / Q000187:drug effects / Q000378:metabolism; D004705:Endocytosis / Q000187:drug effects / Q000235:genetics; D004871:Erbium / Q000737:chemistry*; D005459:Fluorides / Q000737:chemistry*; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D008024:Ligands; D008163:Luminescent Measurements; D057054:Molecular Imaging / Q000379:methods*; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity; D011108:Polymers / Q000737:chemistry* / Q000378:metabolism* / Q000633:toxicity; D013499:Surface Properties; D015018:Ytterbium / Q000737:chemistry*; D015019:Yttrium / Q000737:chemistry*
chemical_list: D002966:Clathrin; D008024:Ligands; D011108:Polymers; C525362:sodium yttriumtetrafluoride; D015019:Yttrium; D004871:Erbium; D015018:Ytterbium; D005459:Fluorides; D002746:Chlorpromazine