Pollinosis is one of serious health problems in Japan. The unbalance of the level between IgG and IgE is thought to be a cause of allergy. Enhancement of IgG production or suppression of IgE production is, therefore, effective for the treatment of allergy. CpG DNA drug has a potential to induce IgG or to suppress IgE production through the interaction with TLR9 followed by interleukin-6 or interferon induction. We found that action of CpG DNA drug can be changed or can be regulated by nanoparticles. Here, this paper introduces CpG DNA delivery by using nanoparticles for the treatment of pollinosis.
We describe a rational design strategy to develop a latent ratiometric fluorescent pH probe from self-assembled seminaphthorhodafluor (SNARF) derivatives in aqueous conditions. Analysis of the characteristics of SNARF derivatives with protected phenolic groups allowed classification of the threshold between the assembled and monomeric states according to the Hansch–Fujita hydrophobic parameters for a substituent inserted as a SNARFOH phenolic-protecting group. As the application of tunable small-molecule aggregation and disaggregation, the enzyme activated latent ratiometric fluorescent pH probes were designed and characterized. Furthermore, the intracellular application of as a latent ratiometric fluorescent pH probe were demonstrated.
Several nanoparticles have ability to reach the mouse brain when these nanoparticles are inhaled, intravenously/ intraperitoneally administered, or applied on the skin. However, it is unknown whether penetrated nanoparticles affect neuronal activity, although nanoparticles' distributions in the brain tissue were reported. It may be difficult to understand the neuronal toxicological effects and mechanisms of nanoparticles in vivo directly, because most particles distribute in other organs, and penetrated particles localize in small tissue area into the brain. Therefore, we propose bottom-up brain model which combined with cellular assays for understanding the toxicological effects. In this report, we present brief summary of examinations about quantum dots with the bottom-up model.
We construct the gene analysis system based on toehold-mediated strand exchange reaction on graphene oxide (GO). Fluorescent dye-labeled probe DNA was indirectly immobilized on fluorescence-quenching GO through a capture DNA. When targets were added, probes were released from the GO surface. We achieved higher emission recovery and more signal contrast relative to conventional methods that are based on direct adsorption of probe DNA.
The technologies for X-ray computed tomography (CT) or fluorescence imaging has been intensively developed in recent years. The X-ray CT imaging has high quantitative sensitivity because X-ray absorption coefficients are proportional to the volume of contrast agents. The X-ray CT imaging with gold nanoparticles as contrast agents has recently reported. Gold is superior to conventional iodine-base compounds contrast agent in term of X-ray absorption coefficients 1）. As the resolution of X-ray CT imaging is around several tens of micrometers, the CT imaging can visualize at levels ranging from small tissues to whole body by high penetrative power of X-rays. Quantum dots (QDs) is one of recently-developed fluorescence nanoparticles and used for various biological imaging. The brightness and photostability of QDs are much greater than those of conventional fluorescent dyes or proteins. Fluorescence imaging has the resolution with hundreds of nanometer and high quantitative sensitivity because the fluorescence signal intensity is proportional to the intensity of the photon excitation energy. However, as the fluorescence imaging was affected by optical scatter and absorption in cells or tissues, tissue permeability of fluorescence is not well. Therefore, fluorescence imaging is suitable to visualize at levels ranging from molecular to small tissues. It is thought that the technology integration of both advantages for X-ray CT and fluorescence imaging greatly contribute to development of medical imaging with high accuracy and highly-quantitative sensitivity at levels ranging from molecular to whole body. Here we developed silica-coated gold nanoparticles and silica-coated QDs nanoparticles and report dual imaging of lymph node with these nanoparticles. To make silica-coated gold nanoparticles and silica-coated QD nanoparticles, silica coating was performed using a modified Stöber method based on the sol-gel method [2]. Gold nanoparticles or QDs were mixed with tetraethylorthosilicate (TEOS)/ethanol. Then a sodium hydroxide solution (a catalyst for the sol-gel reaction of TEOS) was mixed with the solution containing gold nanoparticles and TEOS or QDs and TEOS. As silica is relatively biocompatible material, it is expected that the silica-shell prevents aggregation and allergy of core in vivo. Recently, lymph node diagnosis for cancer surgery is growing in importance because cancer cells metastasize to other parts of the body via lymph vessels or blood vessels. To apply these silica-coated nanoparticles to lymph node diagnosis, we injected these nanoparticles mixture into lower legs of mice. Then X-ray CT or fluorescence imaging was performed to examine distribution of these nanoparticles at subcutaneous of lower legs. The results showed that both nanoparticles were localized to lymph node via lymph vessels. Distribution of both agents was almost
FAM chromophore-modified oligonucleotide of the part of human telomere sequence, 5’-TAG GGT TAG GGT TAG GGT TAG GG-3’, attached to peptide linker carrying TAMRA chromophore and biotin was synthesized to monitor Na+ in living cell as a first trial. Fluorescence intensity (F.I.) at 518 nm of the obtained conjugate derived from FAM decreased and at the same time fluorescence intensity at 585 nm derived from TAMRA increased upon addition of NaCl or KCl. This behavior comes from tetraplex structure formation of the conjugate and subsequently increasing FRET efficiency in the presence of Na+ or K+. Fluorescence ratio obtained from F.I. at 585 nm divided by F.I. at 518 nm under 200 mM NaCl was larger than that under 200 mM KCl. This result is in agreement with our expatiation that its tetraplex structure with K+ is hybrid-1 form where two chromophores are located farther away position than that of basket from induced by Na+ as confirmed with its circler dichroism spectra in the presence of Na+ or K+. However, dissociation constraint for Na+ was over 10-times larger than that for K+. When one can find out the oligonucleotide sequence carrying preference for Na+ rather than K+, fluorescence reagent will be realized to permit a monitoring of Na+ under excess amounts of K+ which is suitable for an outside cell.
It has been demonstrated that β-1,3-glucans can form novel complexes with homo oligodeoxynucleotides(ODNs) via a combination of hydrogen bonding and hydrophobic interactions. Therefore, the complex could be used to deliver an antisense ODN that can rectify abnormalities associated with inflammation. In this study, we show the application of the novel complex consisting of β-1,3-glucan and CpG-DNA for drug delivery system. In-vivo, CpGDNA/ SPG induced robust type interferon responses dependently of Toll-like receptor 9.
MRI contrast agents are effective for shortening the measuring time and enhancement of the detection of signals in the diagnostic process of MRI. The contrast enhanced image is expressed for the difference of nuclear magnetic relaxation rate of protons in a living body. MRI contrast agent enhances the contrast of the bright and dark areas by reducing the magnetic relaxation of protons. Currently, main components of γ-Fe2O3 and Fe3O4 have been used for MRI contrast agents to emphasize the relaxation time of T2 in the clinical scene. However, the relationship between these MRI relaxivity and physical properties has not been revealed. In this study, we synthesized CoxFe3-xO4 (x = 0.2, 0.4, 0.6, 0.8) and CoFe2O･nSiO2 ( n =1,3,6 and removed Si) nanoparticles, and evaluated MRI enhance effect of these samples.