Abstract
In this report, monodisperse upconversion NaYF4:Yb3+/Er3+ nanoparticles with superior optical properties were synthesized by the oleic acid-stabilized high-temperature co-precipitation of lanthanide chlorides in octadec-1-ene as a high-boiling organic solvent. To render the particles with biocompatibility and colloidal stability in bioanalytically relevant phosphate buffered saline (PBS), they were modified by using in-house synthesized poly(ethylene glycol)-neridronate (PEG-Ner), a bisphosponate. The NaYF4:Yb3+/Er3+@PEG nanoparticles showed excellent long-term stability in PBS and/or albumin without any aggregation or morphology transformation. The in vitro cytotoxicity of the nanoparticles was evaluated using primary fibroblasts (HF) and a cell line derived from human cervical carcinoma (HeLa). The particles were subsequently modified by using Bolton-Hunter-hydroxybisphosphonate to enable radiolabeling with 125I for single-photon emission computed tomography/computed tomography (SPECT/CT) bimodal imaging to monitor the biodistribution of the nanoparticles in non-tumor mice. The bimodal upconversion 125I-radiolabeled NaYF4:Yb3+/Er3+@PEG nanoparticles are prospective for near-infrared (NIR) photothermal/photodynamic and SPECT/CT cancer theranostics.
Highlights
Accurate imaging of contrast agents and therapeutics inside diseased cells deep within the body and the determination of their location are of crucial importance for the diagnosis of various diseases.[1,2] Radionuclide-based single-photon emission computed tomography (SPECT) on an anatomical background of computed tomography (CT) provides highly sensitive and quantitative molecular imaging
Colloidally stable upconversion particles in phosphate buffered saline (PBS): modification of NaYF4:Yb3+/Er3+ with poly(ethylene glycol)-neridronate (PEG-Ner) Upconversion NaYF4:Yb3+/Er3+ nanoparticles of superior quality were synthesized by the high-temperature co-precipitation of lanthanide chlorides in a high-boiling solvent at 300 °C; oleic acid served as a stabilizer
The NaYF4:Yb3+/ Er3+ particles were hydrophobic due to the presence of the oleic acid capping ligand. Such particles cannot be dispersed in aqueous media, as required in biological systems
Summary
Accurate imaging of contrast agents and therapeutics inside diseased cells deep within the body and the determination of their location are of crucial importance for the diagnosis of various diseases.[1,2] Radionuclide-based single-photon emission computed tomography (SPECT) on an anatomical background of computed tomography (CT) provides highly sensitive and quantitative molecular imaging. Since the maximum particle absorption (980 nm) falls into the optical window in biological tissues, tissue penetration is relatively deep; those wavelengths are not absorbed by hemoproteins.[10] Other advantages of the particles include minimum autofluorescence, a large anti-Stokes shift, narrow emission bandwidths and low scattering, which strongly decreases with increasing wavelength (∼1/λ4).[11] The upconversion nanoparticles composed of a NaYF4 crystal host lattice and doped by an optically active Yb3+/Er3+ ion pair are able after the sequential absorption of two or more low-energy NIR photons to convert them into high-energy visible emission, which may subsequently serve for efficient photodynamic or photothermal therapy in situ.[12,13] Upconversion nanoparticles are highly promising for various applications in biological fields, such as in vitro cell labelling,[14] in vivo multimodal imaging and cell tracking,[15] controlled drug delivery,[16] photodynamic therapy, photoacoustic therapy,[17] and photothermal therapy.[18,19] phototherapy generating singlet oxygen in cancer tissue is a very promising theranostic method for clinical oncology.[20]
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