Horák D., Kostiv U., Proks V., Jirák D.
Institute of Macromolecular Chemistry AS CR, CZ
Keywords: carcinoma, magnetic, nanoparticles, RGDS, TAT, upconversion
Specific targeting and in vivo visualization of cancer cells is of crucial importance for early detection and treatment of cancer. We have developed monodisperse poly(ethylene glycol) (PEG)-modified SiO2-coated Fe3O4 superparamagnetic nanoparticles [1] with size tuned from 6 to 20 nm and spherical shape from Fe(III) oleate (Figure 1 a). Similarly, novel monodisperse spherical or hexagonal NaYF4:Yb3+/Er3+ and NaGdF4:Yb3+/Er3+ upconversion nanoparticles [2] with the size controlled in 16-266 nm range were obtained by oleic acid-stabilized thermal decomposition of lanthanide chlorides in the presence of NaF (Figure 1 b). Nanoparticles synthesized in the presence of organic capping ligands are in general poorly dispersible in aqueous media, which limits their usage in medicine. To render the originally hydrophobic particles with hydrophilic properties, the surface was modified by hydrolysis/condensation of tetramethyl orthosilicate/(3-aminopropyl)triethoxysilane using a water-in-oil reverse microemulsion and reaction with 4-pentynoic acid. The following conjugation of the NaYF4:Yb3+/Er3+&SiO2-alkyne particles with the azido-functionalized cell-adhesive RGDS and cell-penetrating TAT peptides via Cu(I)-catalyzed cycloaddition (click reaction) produced a new generation of biomimetic luminescent biomarkers, which target cell nuclei or membranes (Figure 2). Physicochemical properties of the nanoparticles were determined by transmission electron microscopy, FTIR spectroscopy, confocal inverted fluorescence microscopy, and/or magnetic resonance imaging (MRI). Upconversion nanoparticles were specifically targeted to the human epitheloid cervix carcinoma (HeLa) cells. While the TAT&SiO2-NaYF4:Yb3+/Er3+ particles predominantly crossed the cell membrane and accumulated in the cell cytoplasm (Figure 3 a), the RGDS&SiO2-NaYF4:Yb3+/Er3+ particles were localized mainly on the cell plasma membrane due to specific binding of the peptide to the corresponding integrin (Figure 3 b). Excellent visibility and facile monitoring of the RGDS- and TAT-conjugated NaYF4:Yb3+/Er3+ nanoparticles in the living cells is very promising for perspective use of the drug-conjugated upconversion nanoparticles in theranostic applications enabling targeting and imaging of specific tumor phenotypes [3]. The upconversion NaYF4:Yb3+/Er3+ nanoparticles have also attracted a lot of attention as a promising photosensitizer carrier for a deep tissue photodynamic therapy (PDT). The nanoparticles were conjugated to Zn carboxyphthalocyanine and intravenously administered in athymic nude mice with xenotransplanted human tumor (Figure 4 a). The tumor necrotized after IR PDT using a 980-nm laser (160 J/cm2; Figure 4 b). Moreover, NaGdF4:Yb3+/Er3+ nanoparticles could combine upconversion emission with external magnetic manipulation and MRI. Combination of these two modalities renders hybrid magnetic-upconversion systems with potential applications in photothermal and photodynamic therapy, MRI, and biosensing. Financial support of the Czech Science Foundation (No. 15-01897S) and RECOOP HST Association and the participating Cedars-Sinai Medical Center is acknowledged. References 1. Kostiv U. et al., RSC Advances, submitted. 2. Kostiv U. et al., Nanoscale 7, 18096-18104 (2015). 3. Kostiv U. et al., ACS Appl. Mater. Interfaces 8, 20422-20431 (2016).
Journal: TechConnect Briefs
Volume: 3, Biotech, Biomaterials and Biomedical: TechConnect Briefs 2017
Published: May 14, 2017
Pages: 114 - 117
Industry sector: Medical & Biotech
Topic: Diagnostics & Bioimaging
ISBN: 978-0-9988782-0-1