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 (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

Upconverting luminescent lanthanide-doped nanoparticles (UCNP) belong to promising new materials that absorb infrared light able to penetrate in the deep tissue level, while emitting photons in the visible or ultraviolet region, which makes them favorable for bioimaging and cell labeling. Here, we have prepared upconverting NaYF4:Yb,Er@NaYF4:Nd core-shell nanoparticles, which were coated with copolymers of N,N-dimethylacrylamide (DMA) and 2-(acryloylamino)-2-methylpropane-1-sulfonic acid (AMPS) or tert-butyl [2-(acryloylamino)ethyl]carbamate (AEC-Boc) with negative or positive charges, respectively. The copolymers were synthesized by a reversible addition-fragmentation chain transfer (RAFT) polymerization, reaching Mn ~ 11 kDa and containing ~ 5 mol% of reactive groups. All copolymers contained bisphosphonate end-groups to be firmly anchored on the surface of NaYF4:Yb,Er@NaYF4:Nd core-shell nanoparticles. To compare properties of polymer coatings, poly(ethylene glycol)-coated and neat UCNP were used as a control. UCNP with various charges were then studied as labels of carcinoma cells, including human hepatocellular carcinoma HepG2, human cervical cancer HeLa, and rat insulinoma INS-1E cells. All the particles proved to be biocompatible (nontoxic); depending on their ξ-potential, the ability to penetrate the cells differed. This ability together with the upconversion luminescence are basic prerequisites for application of particles in photodynamic therapy (PDT) of various tumors, where emission of nanoparticles in visible light range at ~ 650 nm excites photosensitizer.

• MeSH
• akrylamidy chemie   MeSH
• buňky Hep G2 MeSH
• fluorescenční barviva chemie   MeSH
• fluoridy chemie   MeSH
• HeLa buňky MeSH
• lidé MeSH
• nádory diagnostické zobrazování   MeSH
• nanočástice chemie   MeSH
• optické zobrazování metody   MeSH
• ytrium chemie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• akrylamidy MeSH
• fluorescenční barviva MeSH
• fluoridy MeSH
• poly(N,N-dimethylacrylamide) MeSH Prohlížeč
• sodium yttriumtetrafluoride MeSH Prohlížeč
• ytrium MeSH

Capsid surface shielding of adenovirus vectors with synthetic polymers is an emerging technology to reduce unwanted interactions of the vector particles with cellular and non-cellular host components. While it has been shown that attachment of shielding polymers allows prevention of undesired interactions, it has become evident that a shield which is covalently attached to the vector surface can negatively affect gene transfer efficiency. Reasons are not only a limited receptor-binding ability of the shielded vectors but also a disturbance of intracellular trafficking processes, the latter depending on the interaction of the vector surface with the cellular transport machinery. A solution might be the development of bioresponsive shields that are stably maintained outside the host cell but released upon cell entry to allow for efficient gene delivery to the nucleus. Here we provide a systematic comparison of irreversible versus bioresponsive shields based on synthetic N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers. In addition, the chemical strategy used for generation of the shield allowed for a traceless bioresponsive shielding, i.e., polymers could be released from the vector particles without leaving residual linker residues. Our data demonstrated that only a bioresponsive shield maintained the high gene transfer efficiency of adenovirus vectors both in vitro and in vivo. As an example for bioresponsive HPMA copolymer release, we analyzed the in vivo gene transfer in the liver. We demonstrated that both the copolymer's charge and the mode of shielding (irreversible versus traceless bioresponsive) profoundly affected liver gene transfer and that traceless bioresponsive shielding with positively charged HPMA copolymers mediated FX independent transduction of hepatocytes. In addition, we demonstrated that shielding with HPMA copolymers can mediate a prolonged blood circulation of vector particles in mice. Our results have significant implications for the future design of polymer-shielded Ad and provide a deeper insight into the interaction of shielded adenovirus vector particles with the host after systemic delivery.

• MeSH
• fluorometrie MeSH
• genetické vektory genetika   metabolismus   MeSH
• imunohistochemie MeSH
• konfokální mikroskopie MeSH
• methakryláty chemie   metabolismus   MeSH
• molekulární struktura MeSH
• myši inbrední BALB C MeSH
• myši MeSH
• neparametrická statistika MeSH
• organické látky MeSH
• polymerázová řetězová reakce MeSH
• signální transdukce fyziologie   MeSH
• technika přenosu genů * MeSH
• virové plášťové proteiny metabolismus   MeSH
• western blotting MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• hexon capsid protein, Adenovirus MeSH Prohlížeč
• hydroxypropyl methacrylate MeSH Prohlížeč
• methakryláty MeSH
• organické látky MeSH
• SYBR Green II MeSH Prohlížeč
• virové plášťové proteiny MeSH