Nejvíce citovaný článek - PubMed ID 29105372
Phthalocyanine-Conjugated Upconversion NaYF4 :Yb3+ /Er3+ @SiO2 Nanospheres for NIR-Triggered Photodynamic Therapy in a Tumor Mouse Model
Photodynamic therapy (PDT) has the potential to cure pancreatic cancer with minimal side effects. Visible wavelengths are primarily used to activate hydrophobic photosensitizers, but in clinical practice, these wavelengths do not sufficiently penetrate deeper localized tumor cells. In this work, NaYF4:Yb3+,Er3+,Fe2+ upconversion nanoparticles (UCNPs) were coated with polymer and labeled with meta-tetra(hydroxyphenyl)chlorin (mTHPC; temoporfin) to enable near-infrared light (NIR)-triggered PDT of pancreatic cancer. The coating consisted of alendronate-terminated poly[N,N-dimethylacrylamide-co-2-aminoethylacrylamide]-graft-poly(ethylene glycol) [P(DMA-AEM)-PEG-Ale] to ensure the chemical and colloidal stability of the particles in aqueous physiological fluids, thereby also improving the therapeutic efficacy. The designed particles were well tolerated by the human pancreatic adenocarcinoma cell lines CAPAN-2, PANC-1, and PA-TU-8902. After intratumoral injection of mTHPC-conjugated polymer-coated UCNPs and subsequent exposure to 980 nm NIR light, excellent PDT efficacy was achieved in tumor-bearing mice.
- MeSH
- akrylamidy chemie MeSH
- fotochemoterapie * metody MeSH
- fotosenzibilizující látky * chemie farmakologie MeSH
- infračervené záření MeSH
- koloidy chemie MeSH
- lidé MeSH
- mesoporfyriny * chemie farmakologie MeSH
- myši inbrední BALB C MeSH
- myši nahé MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- nádory slinivky břišní * farmakoterapie patologie MeSH
- nanočástice chemie MeSH
- polyethylenglykoly * chemie MeSH
- polymery chemie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- akrylamidy MeSH
- fotosenzibilizující látky * MeSH
- koloidy MeSH
- mesoporfyriny * MeSH
- polyethylenglykoly * MeSH
- polymery MeSH
- temoporfin MeSH Prohlížeč
Upconverting nanoparticles are interesting materials that have the potential for use in many applications ranging from solar energy harvesting to biosensing, light-triggered drug delivery, and photodynamic therapy (PDT). One of the main requirements for the particles is their surface modification, in our case using poly(methyl vinyl ether-alt-maleic acid) (PMVEMA) and temoporfin (THPC) photosensitizer to ensure the colloidal and chemical stability of the particles in aqueous media and the formation of singlet oxygen after NIR irradiation, respectively. Codoping of Fe2+, Yb3+, and Er3+ ions in the NaYF4 host induced upconversion emission of particles in the red region, which is dominant for achieving direct excitation of THPC. Novel monodisperse PMVEMA-coated upconversion NaYF4:Yb3+,Er3+,Fe2+ nanoparticles (UCNPs) with chemically bonded THPC were found to efficiently transfer energy and generate singlet oxygen. The cytotoxicity of the UCNPs was determined in the human pancreatic adenocarcinoma cell lines Capan-2, PANC-01, and PA-TU-8902. In vitro data demonstrated enhanced uptake of UCNP@PMVEMA-THPC particles by rat INS-1E insulinoma cells, followed by significant cell destruction after excitation with a 980 nm laser. Intratumoral administration of these nanoconjugates into a mouse model of human pancreatic adenocarcinoma caused extensive necrosis at the tumor site, followed by tumor suppression after NIR-induced PDT. In vitro and in vivo results thus suggest that this nanoconjugate is a promising candidate for NIR-induced PDT of cancer.
- Klíčová slova
- pancreatic tumor, photodynamic therapy, temoporfin, upconversion,
- Publikační typ
- časopisecké články MeSH
Upconverting nanoparticles are attracting extensive interest as a multimodal imaging tool. In this work, we report on the synthesis and characterization of gadolinium-enriched upconverting nanoparticles for bimodal magnetic resonance and optical luminescence imaging. NaYF4:Gd3+,Yb3+,Tm3+ core upconverting nanoparticles were obtained by a thermal coprecipitation of lanthanide oleate precursors in the presence of oleic acid as a stabilizer. With the aim of improving the upconversion emission and increasing the amount of Gd3+ ions on the nanoparticle surface, a 2.5 nm NaGdF4 shell was grown by the epitaxial layer-by-layer strategy, resulting in the 26 nm core-shell nanoparticles. Both core and core-shell nanoparticles were coated with poly(ethylene glycol) (PEG)-neridronate (PEG-Ner) to have stable and well-dispersed upconverting nanoparticles in a biological medium. FTIR spectroscopy and thermogravimetric analysis indicated the presence of ∼20 wt % of PEG-Ner on the nanoparticle surface. The addition of inert NaGdF4 shell resulted in a total 26-fold enhancement of the emission under 980 nm excitation and also affected the T 1 and T 2 relaxation times. Both r 1 and r 2 relaxivities of PEG-Ner-modified nanoparticles were much higher compared to those of non-PEGylated particles, thus manifesting their potential as a diagnostic tool for magnetic resonance imaging. Together with the enhanced luminescence efficiency, upconverting nanoparticles might represent an efficient probe for bimodal in vitro and in vivo imaging of cells in regenerative medicine, drug delivery, and/or photodynamic therapy.
- Publikační typ
- časopisecké články MeSH
Development of upconverting nanomaterials which are able to emit visible light upon near-infrared excitation opens a wide range of potential applications. Because of their remarkable photostability, they are widely used in bioimaging, optogenetics, and optoelectronics. In this work, we demonstrate the influence of several experimental conditions as well as a dopant concentration on the luminescence properties of upconverting nanocrystals (UPNCs) that need to be taken into account for their efficient use in the practical applications. We found that not only nanoparticle architecture affects the optical properties of UPNCs, but also factors such as sample concentration, excitation light power density, and temperature may influence the green-to-red emission ratio. We performed studies on both the single-nanoparticle and ensemble levels over a broad concentration range and found the heterogeneity in the optical properties of UPNCs with low dopant concentrations.
- Publikační typ
- časopisecké články MeSH
Lanthanide-doped upconversion nanoparticles (UCNPs) have a unique capability of upconverting near-infrared (NIR) excitation into ultraviolet, visible, and NIR emission. Conventional UCNPs composed of NaYF4:Yb3+/Er3+(Tm3+) are excited by NIR light at 980 nm, where undesirable absorption by water can cause overheating or damage of living tissues and reduce nanoparticle luminescence. Incorporation of Nd3+ ions into the UCNP lattice shifts the excitation wavelength to 808 nm, where absorption of water is minimal. Herein, core-shell NaYF4:Yb3+/Er3+@NaYF4:Nd3+ nanoparticles, which are doubly doped by sensitizers (Yb3+ and Nd3+) and an activator (Er3+) in the host NaYF4 matrix, were synthesized by high-temperature coprecipitation of lanthanide chlorides in the presence of oleic acid as a stabilizer. Uniform core (24 nm) and core-shell particles with tunable shell thickness (~0.5-4 nm) were thoroughly characterized by transmission electron microscopy (TEM), energy-dispersive analysis, selected area electron diffraction, and photoluminescence emission spectra at 808 and 980 nm excitation. To ensure dispersibility of the particles in biologically relevant media, they were coated by in-house synthesized poly(ethylene glycol) (PEG)-neridronate terminated with an alkyne (Alk). The stability of the NaYF4:Yb3+/Er3+@NaYF4:Nd3+-PEG-Alk nanoparticles in water or 0.01 M PBS and the presence of PEG on the surface were determined by dynamic light scattering, ζ-potential measurements, thermogravimetric analysis, and FTIR spectroscopy. Finally, the adhesive azidopentanoyl-modified GGGRGDSGGGY-NH2 (RGDS) peptide was immobilized on the NaYF4:Yb3+/Er3+@NaYF4:Nd3+-PEG-Alk particles via Cu(I)-catalyzed azide-alkyne cycloaddition. The toxicity of the unmodified core-shell NaYF4:Yb3+/Er3+@NaYF4:Nd3+, NaYF4:Yb3+/Er3+@NaYF4:Nd3+-PEG-Alk, and NaYF4:Yb3+/Er3+@NaYF4:Nd3+-PEG-RGDS nanoparticles on both Hep-G2 and HeLa cells was determined, confirming no adverse effect on their survival and proliferation. The interaction of the nanoparticles with Hep-G2 cells was monitored by confocal microscopy at both 808 and 980 nm excitation. The NaYF4:Yb3+/Er3+@NaYF4:Nd3+-PEG-RGDS nanoparticles were localized on the cell membranes due to specific binding of the RGDS peptide to integrins, in contrast to the NaYF4:Yb3+/Er3+@NaYF4:Nd3+-PEG-Alk particles, which were not engulfed by the cells. The NaYF4:Yb3+/Er3+@NaYF4:Nd3+-PEG-RGDS nanoparticles thus appear to be promising as a new non-invasive probe for specific bioimaging of cells and tissues. This development makes the nanoparticles useful for diagnostic and/or, after immobilization of a bioactive compound, even theranostic applications in the treatment of various fatal diseases.
- Klíčová slova
- 808 nm excitation, Hep-G2 and HeLa cells, PEG-neridronate, RGDS peptide, core-shell, luminescence, upconversion nanoparticles,
- Publikační typ
- časopisecké články MeSH
Magnetic and temperature-sensitive solid lipid particles (mag. SLPs) were prepared in the presence of oleic acid-coated iron oxide (IO-OA) nanoparticles with 1-tetradecanol and poly(ethylene oxide)-block-poly(ε-caprolactone) as lipid and stabilizing surfactant-like agents, respectively. The particles, typically ~850 nm in hydrodynamic size, showed heat dissipation under the applied alternating magnetic field. Cytotoxic activity of the mag.SLPs, non-magnetic SLPs, and iron oxide nanoparticles was compared concerning the mammalian cancer cell lines and their drug-resistant counterparts using trypan blue exclusion test and MTT assay. The mag.SLPs exhibited dose-dependent cytotoxicity against human leukemia cell lines growing in suspension (Jurkat and HL-60/wt), as well as the doxorubicin (Dox)- and vincristine-resistant HL-60 sublines. The mag.SLPs showed higher cytotoxicity toward drug-resistant sublines as compared to Dox. The human glioblastoma cell line U251 growing in a monolayer culture was also sensitive to mag.SLPs cytotoxicity. Staining of U251 cells with the fluorescent dyes Hoechst 33342 and propidium iodide (PI) revealed that mag.SLPs treatment resulted in an increased number of cells with condensed chromatin and/or fragmented nuclei as well as with blebbing of the plasma membranes. While the Hoechst 33342 staining of cell suggested the pro-apoptotic activity of the particles, the PI staining indicated the pro-necrotic changes in the target cells. These conclusions were confirmed by Western blot analysis of apoptosis-related proteins, study of DNA fragmentation (DNA laddering due to the inter-nucleosomal cleavage and DNA comets due to single strand breaks), as well as by FACS analysis of the patterns of cell cycle distribution (pre-G1 phase) and Annexin V/PI staining of the treated Jurkat cells. The induction of apoptosis or necrosis by the particles used to treat Jurkat cells depended on the dose of the particles. Production of the reactive oxygen species (ROS) was proposed as a potential mechanism of mag.SLPs-induced cytotoxicity. Accordingly, hydrogen peroxide and superoxide radical levels in mag.SLPs-treated Jurkat leukemic cells were increased by ~20-40 and ~70%, respectively. In contrast, the non-magnetic SLPs and neat iron oxides did not influence ROS levels significantly. Thus, the developed mag.SLPs can be used for effective killing of human tumor cells, including drug-resistant ones.
