Jinmyung Cha

Estimating the density of fluorescent nanoparticles in the primo vessels in the fourth ventricle and the spinal cord of a rat

The primo vascular system is a novel circulatory system forming a network throughout an animals body. Primo vessels were recently observed in the fourth ventricle of the brain and in the spinal cord of a rat by using fluorescent nanoparticles. In order to quantify the nanoparticles in the primo vessels, we measured the florescence of the nanoparticles and calibrated the measurements by using a reference suspension. We removed the noise due to autofluorescence with the technique of multispectral imaging. The line densities of nanoparticles and the contrast values of their images were, respectively, 0.5 ± 0.5 ng/mm and 0.7 ± 0.5 for primo vessels in the fourth ventricle, and 1.3 ± 0.6 ng/mm and 1.4 ± 0.2 for primo vessels in the spinal cord. The data obtained from and the procedures used in this work could be useful in evaluating the feasibility of using nanoparticles as a contrast agent during MRI or CT imaging of primo vessels in the brain or the spinal cord.

Dual-Modal Nanoprobes for Imaging of Mesenchymal Stem Cell Transplant by MRI and Fluorescence Imaging

Objective To determine the feasibility of labeling human mesenchymal stem cells (hMSCs) with bifunctional nanoparticles and assessing their potential as imaging probes in the monitoring of hMSC transplantation. Materials and Methods The T1 and T2 relaxivities of the nanoparticles (MNP@SiO2[RITC]-PEG) were measured at 1.5T and 3T magnetic resonance scanner. Using hMSCs and the nanoparticles, labeling efficiency, toxicity, and proliferation were assessed. Confocal laser scanning microscopy and transmission electron microscopy were used to specify the intracellular localization of the endocytosed iron nanoparticles. We also observed in vitro and in vivo visualization of the labeled hMSCs with a 3T MR scanner and optical imaging. Results MNP@SiO2(RITC)-PEG showed both superparamagnetic and fluorescent properties. The r1 and r2 relaxivity values of the MNP@SiO2(RITC)-PEG were 0.33 and 398 mM-1 s-1 at 1.5T, respectively, and 0.29 and 453 mM-1 s-1 at 3T, respectively. The effective internalization of MNP@SiO2(RITC)-PEG into hMSCs was observed by confocal laser scanning fluorescence microscopy. The transmission electron microscopy images showed that MNP@SiO2(RITC)-PEG was internalized into the cells and mainly resided in the cytoplasm. The viability and proliferation of MNP@SiO2(RITC)-PEG-labeled hMSCs were not significantly different from the control cells. MNP@SiO2(RITC)-PEG-labeled hMSCs were observed in vitro and in vivo with optical and MR imaging. Conclusion MNP@SiO2(RITC)-PEG can be a useful contrast agent for stem cell imaging, which is suitable for a bimodal detection by MRI and optical imaging.

A simple method to synthesize multifunctional silica nanocomposites, NPs@SiO2, using polyvinylpyrrolidone (PVP) as a mediator

The well-investigated method to prepare various nanoparticles is a thermolysis method in hot organic solutions. These nanoparticles are usually dispersible in nonpolar organic solvents, which sometimes causes problem to overcoat them with silica due to the polar alcoholic solvent in the silica forming process. We have developed a general procedure to incorporate high quality nanoparticles into silica beads. Organic-dispersible nanoparticles do not form precipitates in alcoholic solution in the presence of hydrophilic polyvinylpyrrolidone (PVP), and successive addition of TEOS with a basic catalyst can generate silica coating on nanocrystals. The PVP stabilized nanoparticles can also be easily adsorbed on the amino-functionalized silica bead surface to form interesting core-shell type structures. Many different nanoparticles from the thermolysis can be used in our preparation method, and these multifunctional silica nanocomposites are expected to be utilized in many applied fields where wettability, biocompatibility and ease of surface modification are very critical.

Synthesis of various magnetite nanoparticles through simple phase transformation and their shape-dependent magnetic properties

Shape-controlled synthesis of magnetite nanoparticles has been successfully carried out through simple phase transformation via a modified polyol process using akaganeite (β-FeOOH) as the precursor. Different shapes of magnetite nanoparticles, including solid nanospheres and solid and hollow nanoellipsoids, could be obtained by either adding the appropriate amount of sodium acetate (NaOAc) or using the anion exchange of β-FeOOH. NaOAc makes it possible to retain the rod-like shape of the precursor material during the phase transformation by coordinating the surface and controlling the basic pH to slow down dissolution–recrystallization mechanism. It is also proposed that chloride ions in the β-FeOOH structure play a key role in the formation of hollow structure. The shape-dependent magnetic properties were investigated using a magnetic property measurement system at 300 K. All magnetite nanoparticles exhibited ferromagnetic behaviour with different values of saturation magnetization (Ms) and coercivity (Hc), and these values were highly depend on the shape of the nanoparticles due to their different grain size, spin disorder, shape, and surface anisotropy.

Solid-state phase transformation mechanism for formation of magnetic multi-granule nanoclusters

Magnetic multi-granule nanoclusters (MGNCs) were easily formed by the simple reaction of FeCl3 in ethylene glycol, which served as both the solvent and reductant, in the presence of sodium acetate. Simple refluxing within glassware at atmospheric pressure allowed us to monitor changes in the color of reaction mixtures and isolate intermediates to be characterized. On the basis of these observations, we could suggest a new mechanism of solid-state phase transformation after the hydrolysis/condensation of FeCl3 along with the partial reduction of Fe3+ to Fe2+ by ethylene glycol. The size of MGNCs could be precisely and reproducibly controlled from 50 to 500 nm by varying the reaction conditions. These MGNCs exhibited relatively high MS values of 73–85 emu g−1 and ferrimagnetic properties, but they were stably dispersed in the solution via a strong interaction between solvent molecules and surface functional groups; this interaction overcame the magnetic interactions between particles that caused the formation of aggregates.

Primo Vessel Inside a Lymph Vessel Emerging From a Cancer Tissue

Primo vessels were observed inside the lymph vessels near the caudal vena cava of a rabbit and a rat and in the thoracic lymph duct of a mouse. In the current work we found a primo vessel inside the lymph vessel that came out from the tumor tissue of a mouse. A cancer model of a nude mouse was made with human lung cancer cell line NCI-H460. We injected fluorescent nanoparticles into the xenografted tumor tissue and studied their flow in blood, lymph, and primo vessels. Fluorescent nanoparticles flowed through the blood vessels quickly in few minutes, and but slowly in the lymph vessels. The bright fluorescent signals of nanoparticles disappeared within one hour in the blood vessels but remained much longer up to several hours in the case of lymph vessels. We found an exceptional case of lymph vessels that remained bright with fluorescence up to 24 hours. After detailed examination we found that the bright fluorescence was due to a putative primo vessel inside the lymph vessel. This rare observation is consistent with Bong-Han Kims claim on the presence of a primo vascular system in lymph vessels. It provides a significant suggestion on the cancer metastasis through primo vessels and lymph vessels.

Synthesis of Eu3+-doped Gd2O3 in hollow nanoparticle structures by controlled chemical etching with poly(acrylic acid)

Hollow Eu3+:Gd2O3 nanoparticles were easily prepared, without employing templates, from spherical crystalline Eu3+:Gd2O3 nanoparticles (NPs) via the simple etching process induced by the acidic moieties in the sodium salt solution of poly(acrylic acid), PAA-Na. Some portion of carboxylate units in PAA-Na could bind to the surface of Eu3+:Gd2O3 NPs and control the etching rate of Eu3+:Gd2O3 in acidic conditions such that the rate becomes comparable to the cation migration rate within the crystalline NPs, generating hollow Eu3+:Gd2O3 NPs. This controlled etching process in the presence of additional acid after surface treatment of Eu3+:Gd2O3 NPs with PAA-Na, varied the resulting structures from solid NPs to core-shell, core-void-shell, yolk-shell, and finally, hollow NPs. Based on the low r2/r1 value obtained from the relaxation times measured by time-domain nuclear magnetic resonance (TD-NMR) spectrometry and the good photoluminescent properties of hollow Eu3+:Gd2O3 NPs, accelerated development of multimodal nanoprobes and drug delivery vessels is expected, using the various morphological novelties of synthesized Eu-doped Gd2O3 nanoparticles.

Network of the Primo Vascular System in the Rat Hypodermis

Anatomical and histological studies on acupuncture points (acupoints) and meridians have been one of the most important approaches to revealing the mechanism of acupuncture analgesia and therapeutics. However, researchers have not yet reached a conclusion on the exact anatomical structure of the acupuncture meridians. In this chapter, the network of primo-vessels and nodes in rat hypodermis is reported. Fluorescence imaging showed the network of the primo-vascular system on the layer of superficial fascia (stratum fibrosum) that existed around the location of the stomach meridian from the knee to the middle of the tibia about 24 h after the subcutaneous injection of fluorescent nanoparticles at the acupoint ST36. Its fine morphologies were analyzed by using confocal laser scanning microscopy and transmission electron microscopy. The primo-vessel had a sinus (3–4 μm in diameter) surrounded by a layer of cells, and had a bundle-like collagen architecture (covered by a cellular layer) in which collagen fibers were regularly aligned along the longitudinal direction of the primo-vessel. Nanoparticles were also found in the cellular or extracellular layer. Since it seems evident that the primo-vascular system mainly exists in the fascia, a new perspective is needed to investigate the whole mechanism of the propagation of acupoint stimulation through the primo-vascular system in relation to fascia physiology.

Differentiating Blood, Lymph, and Primo Vessels by Residual Time Characteristic of Fluorescent Nanoparticles in a Tumor Model

Fluorescent nanoparticles (FNPs) which were injected into a tumor tissue flowed out through the blood and lymph vessels. The FNPs in blood vessels remained only in the order for few minutes while those in lymph vessels remained for a long time disappearing completely in 25 hours. We found a primo vessel inside a lymph vessel near a blood vessel, and FNPs remained in the primo vessel for longer than 25 hours. In addition, we examined in detail the residual time characteristics of lymph vessels because it could be useful in a future study of fluid dynamical comparison of the three conduits. These residual time characteristics of FNPs in the three kinds of vessels may have implications for the dynamics of nanoparticle drugs for cancer chemotherapy.