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
- Názvy látek
- akrylamidy MeSH
- fotosenzibilizující látky * MeSH
- koloidy MeSH
- mesoporfyriny * MeSH
- polyethylenglykoly * MeSH
- polymery MeSH
- temoporfin MeSH Prohlížeč
The aim of this study was to develop multifunctional magnetic poly(ε-caprolactone) (PCL) mats with antibacterial properties for bone tissue engineering and osteosarcoma prevention. To provide good dispersion of magnetic iron oxide nanoparticles (IONs), they were first grafted with PCL using a novel three-step approach. Then, a series of PCL-based mats containing a fixed amount of ION@PCL particles and an increasing content of ascorbic acid (AA) was prepared by electrospinning. AA is known for increasing osteoblast activity and suppressing osteosarcoma cells. Composites were characterized in terms of morphology, mechanical properties, hydrolytic stability, antibacterial performance, and biocompatibility. AA affected both the fiber diameter and the mechanical properties of the nanocomposites. All produced mats were nontoxic to rat bone marrow-derived mesenchymal cells; however, a composite with 5 wt.% of AA suppressed the initial proliferation of SAOS-2 osteoblast-like cells. Moreover, AA improved antibacterial properties against Staphylococcus aureus and Escherichia coli compared to PCL. Overall, these magnetic composites, reported for the very first time, can be used as scaffolds for both tissue regeneration and osteosarcoma prevention.
- Klíčová slova
- L‐ascorbic acid, iron oxide nanoparticles, nanocomposites, poly(ε‐caprolactone),
- MeSH
- antibakteriální látky chemie farmakologie MeSH
- Escherichia coli účinky léků MeSH
- kosti a kostní tkáň MeSH
- krysa rodu Rattus MeSH
- kyselina askorbová * chemie farmakologie MeSH
- lidé MeSH
- magnetické nanočástice chemie MeSH
- nádorové buněčné linie MeSH
- nanokompozity chemie MeSH
- osteoblasty metabolismus cytologie MeSH
- osteosarkom patologie MeSH
- polyestery * chemie MeSH
- Staphylococcus aureus * účinky léků růst a vývoj MeSH
- testování materiálů MeSH
- tkáňové inženýrství * MeSH
- tkáňové podpůrné struktury chemie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antibakteriální látky MeSH
- kyselina askorbová * MeSH
- magnetické nanočástice MeSH
- polycaprolactone MeSH Prohlížeč
- polyestery * MeSH
In this study, spherical or hexagonal NaYF4:Yb,Er nanoparticles (UCNPs) with sizes of 25 nm (S-UCNPs) and 120 nm (L-UCNPs) were synthesized by high-temperature coprecipitation and subsequently modified with three kinds of polymers. These included poly(ethylene glycol) (PEG) and poly(N,N-dimethylacrylamide-co-2-aminoethylacrylamide) [P(DMA-AEA)] terminated with an alendronate anchoring group, and poly(methyl vinyl ether-co-maleic acid) (PMVEMA). The internalization of nanoparticles by rat mesenchymal stem cells (rMSCs) and C6 cancer cells (rat glial tumor cell line) was visualized by electron microscopy and the cytotoxicity of the UCNPs and their leaches was measured by the real-time proliferation assay. The comet assay was used to determine the oxidative damage of the UCNPs. An in vivo study on mice determined the elimination route and potential accumulation of UCNPs in the body. The results showed that the L- and S-UCNPs were internalized into cells in the lumen of endosomes. The proliferation assay revealed that the L-UCNPs were less toxic than S-UCNPs. The viability of rMSCs incubated with particles decreased in the order S-UCNP@Ale-(PDMA-AEA) > S-UCNP@Ale-PEG > S-UCNPs > S-UCNP@PMVEMA. Similar results were obtained in C6 cells. The oxidative damage measured by the comet assay showed that neat L-UCNPs caused more oxidative damage to rMSCs than all coated UCNPs while no difference was observed in C6 cells. An in vivo study indicated that L-UCNPs were eliminated from the body via the hepatobiliary route; L-UCNP@Ale-PEG particles were almost eliminated from the liver 96 h after intravenous application. Pilot fluorescence imaging confirmed the limited in vivo detection capabilities of the nanoparticles.
- Klíčová slova
- biological applications, toxicity, upconverting nanoparticles,
- MeSH
- krysa rodu Rattus MeSH
- mezenchymální kmenové buňky * metabolismus účinky léků cytologie MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- nanočástice chemie MeSH
- oxidační stres účinky léků MeSH
- polyethylenglykoly chemie MeSH
- velikost částic MeSH
- viabilita buněk účinky léků MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- polyethylenglykoly MeSH
In the fight against antibiotic resistance, which is rising to dangerously high levels worldwide, new strategies based on antibiotic-conjugated biocompatible polymers bound to magnetic nanoparticles that allow the drug to be manipulated and delivered to a specific target are being proposed. Here, we report the direct surface engineering of nontoxic iron oxide nanoparticles (IONs) using biocompatible dextran (Dex) covalently linked to β-cyclodextrin (β-CD) with the ability to form non-covalent complexes with silver-sulfamethazine (SMT-Ag). To achieve a good interaction of β-CD-modified dextran with the surface of the nanoparticles, it was functionalized with diphosphonic acid (DPA) that provides strong binding to Fe atoms. The synthesized polymers and nanoparticles were characterized by various methods, such as nuclear magnetic resonance (NMR), Fourier transform infrared (FTIR) and ultraviolet-visible (UV-Vis) spectroscopies, transmission electron microscopy (TEM), thermogravimetric analysis (TGA), atomic absorption spectroscopy (AAS), dynamic light scattering (DLS), etc. The resulting magnetic ION@DPA-Dex-β-CD-SMT-Ag nanoparticles were colloidally stable in water and contained 24 μg of antibiotic per mg of the particles. When tested for in vitro antimicrobial activity on Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria and fungi (yeast Candida albicans and mold Aspergillus niger), the particles showed promising potential.
- Klíčová slova
- antimicrobial activity, silver-sulfamethazine, superparamagnetic iron oxide nanoparticles, β-cyclodextrin,
- Publikační typ
- časopisecké články MeSH
In this report, upconverting NaYF4:Yb3+,Er3+ nanoparticles (UCNPs) were synthesized by high-temperature coprecipitation of lanthanide chlorides and encapsulated in poly(glycerol monomethacrylate) (PGMMA). The UCNP surface was first treated with hydrophobic penta(propylene glycol) methacrylate phosphate (SIPO) to improve colloidal stability and enable encapsulation by reversible addition-fragmentation chain transfer miniemulsion polymerization (RAFT) of glycidyl methacrylate (GMA) in water, followed by its hydrolysis. The resulting UCNP-containing PGMMA particles (UCNP@PGMMA), hundreds of nanometers in diameter, were thoroughly characterized by transmission (TEM) and scanning electron microscopy (SEM), dynamic light scattering (DLS), infrared (FTIR) and fluorescence emission spectroscopy, and thermogravimetric analysis (TGA) in terms of particle morphology, size, polydispersity, luminescence, and composition. The morphology, typically raspberry-like, depended on the GMA/UCNP weight ratio. Coating of the UCNPs with hydrophilic PGMMA provided the UCNPs with antifouling properties while enhancing chemical stability and reducing the cytotoxicity of neat UCNPs to a non-toxic level. In addition, it will allow the binding of molecules such as photosensitizers, thus expanding the possibilities for use in various biomedical applications.
- Publikační typ
- časopisecké články MeSH
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
In this report, we synthesized hexagonal NaYF4:Yb,Er upconverting nanoparticles (UCNPs) of 171 nm in size with a narrow particle size distribution. To address their colloidal stabi-lity in aqueous media and to incorporate a photosensitizer that can produce reactive singlet oxygen (1O2) to kill tumor cells, UCNPs were conjugated with 6-bromohexanoic acid-functionalized Rose Bengal (RB) and coated with PEG-alendronate (PEG-Ale). The particles were thoroughly characterized by transmission electron microscopy, dynamic light scattering, ATR FTIR, X-ray photoelectron spectroscopy, thermogravimetric analysis, and spectrofluorometry, and 1O2 formation was detected using a 9,10-diphenylanthracene spectrophotometric probe. Cytotoxicity determination on rat mesenchymal stem cells by using the MTT assay showed that neutralization of the large positive surface charge of neat UCNPs with PEG-Ale and the bound RB sensitizer significantly reduced the concentration-dependent cytotoxicity. The presented strategy shows great potential for the use of these particles as a novel agent for the photodynamic therapy of tumors.
- Klíčová slova
- cytotoxicity, nanoparticles, photosensitizer, rose bengal, upcoverting,
- Publikační typ
- časopisecké články MeSH
Upconverting nanoparticles (UCNPs) are of particular interest in nanomedicine for in vivo deep-tissue optical cancer bioimaging due to their efficient cellular uptake dependent on polymer coating. In this study, particles, ca. 25 nm in diameter, were prepared by a high-temperature coprecipitation of lanthanide chlorides. To ensure optimal dispersion of UCNPs in aqueous milieu, they were coated with three different polymers containing reactive groups, i.e., poly(ethylene glycol)-alendronate (PEG-Ale), poly(N,N-dimethylacrylamide-co-2-aminoethylacrylamide)-alendronate (PDMA-Ale), and poly(methyl vinyl ether-co-maleic acid) (PMVEMA). All the particles were characterized by TEM, DLS, FTIR, and spectrofluorometer to determine the morphology, hydrodynamic size and ξ-potential, composition, and upconversion luminescence. The degradability/dissolution of UCNPs in water, PBS, DMEM, or artificial lysosomal fluid (ALF) was evaluated using an ion-selective electrochemical method and UV-Vis spectroscopy. The dissolution that was more pronounced in PBS at elevated temperatures was decelerated by polymer coatings. The dissolution in DMEM was relatively small, but much more pronounced in ALF. PMVEMA with multiple anchoring groups provided better protection against particle dissolution in PBS than PEG-Ale and PDMA-Ale polymers containing only one reactive group. However, the cytotoxicity of the particles depended not only on their ability to rapidly degrade, but also on the type of coating. According to MTT, neat UCNPs and UCNP@PMVEMA were toxic for both rat cells (C6) and rat mesenchymal stem cells (rMSCs), which was in contrast to the UCNP@Ale-PDMA particles that were biocompatible. On the other hand, both the cytotoxicity and uptake of the UCNP@Ale-PEG particles by C6 and rMSCs were low, according to MTT assay and ICP-MS, respectively. This was confirmed by a confocal microscopy, where the neat UCNPs were preferentially internalized by both cell types, followed by the UCNP@PMVEMA, UCNP@Ale-PDMA, and UCNP@Ale-PEG particles. This study provides guidance for the selection of a suitable nanoparticle coating with respect to future biomedical applications where specific behaviors (extracellular deposition vs. cell internalization) are expected.
- Klíčová slova
- degradation, lanthanides, luminescence, nanoparticles, upconversion,
- MeSH
- alendronát MeSH
- krysa rodu Rattus MeSH
- nanočástice * chemie MeSH
- polyethylenglykoly chemie MeSH
- polymery * chemie MeSH
- voda MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- alendronát MeSH
- polyethylenglykoly MeSH
- polymery * MeSH
- voda MeSH
High-quality upconverting NaYF4:Yb3+,Er3+ nanoparticles (UCNPs; 26 nm in diameter) based on lanthanides were synthesized by a high-temperature coprecipitation method. The particles were modified by bisphosphonate-terminated poly(ethylene glycol) (PEG) and Rose Bengal (RB) photosensitizer. The particles were thoroughly characterized using transmission electron microscopy, dynamic light scattering, thermogravimetric analysis, FTIR, and X-ray photoelectron and upconversion luminescence spectroscopy in terms of morphology, hydrodynamic size, composition, and energy transfer to the photosensitizer. Moreover, the singlet oxygen generation from RB-containing UCNPs was investigated using 9,10-diphenylanthracene probe under 980 nm excitation. The cytotoxicity of UCNPs before and after conjugation with RB was evaluated on highly sensitive rat mesenchymal stem cells (rMSCs) and significant differences were found. Correspondingly, consi-derable variations in viability were revealed between the irradiated and non-irradiated rat glioma cell line (C6) exposed to RB-conjugated UCNPs. While the viability of rMSCs was not affected by the presence of UCNPs themselves, the cancer C6 cells were killed after the irradiation at 980 nm due to the reactive oxygen species (ROS) production, thus suggesting the potential of RB-conjugated PEG-modified UCNPs for applications in photodynamic therapy of cancer.
- Klíčová slova
- Rose Bengal, cytotoxicity, nanoparticles, photodynamic therapy, reactive oxygen species, upconverting,
- Publikační typ
- časopisecké články MeSH
Novel Yb,Tb,Nd-doped GdF3 and NaGdF4 nanoparticles were synthesized by a coprecipitation method in ethylene glycol (EG) in the presence of the poly(4-styrenesulfonic acid-co-maleic anhydride) stabilizer. The particle size and morphology, crystal structure, and phase change were controlled by adjusting the PSSMA concentration and source of fluoride anions in the reaction. Doping of Yb3+, Tb3+, and Nd3+ ions in the NaGdF4 host nanoparticles induced luminescence under ultraviolet and near-infrared excitation and high relaxivity in magnetic resonance (MR) imaging (MRI). In vitro toxicity of the nanoparticles and their cellular uptake efficiency were determined in model rat pancreatic β-cells (INS-1E). As the NaGdF4:Yb,Tb,Nd@PSSMA-EG nanoparticles were non-toxic and possessed good luminescence and magnetic properties, they were applicable for in vitro optical and MRI of isolated pancreatic islets in phantoms. The superior contrast was achieved for in vivo T2*-weighted MR images of the islets transplanted under the kidney capsule to mice in preclinical trials.
- Klíčová slova
- MRI, gadolinium fluoride, luminescence, nanoparticles, pancreatic islets, β-cells,
- MeSH
- krysa rodu Rattus MeSH
- Langerhansovy ostrůvky * diagnostické zobrazování MeSH
- luminiscence MeSH
- magnetická rezonanční tomografie metody MeSH
- maleinanhydridy MeSH
- myši MeSH
- nanočástice * chemie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- maleinanhydridy MeSH
