Smart Hybrid Nanocomposite for Photodynamic Inactivation of Cancer Cells with Selectivity.

Photodynamic therapy has been efficiently applied for cancer therapy. Here, we have fabricated the folic acid (FA)- and pheophorbide A (PA)-conjugated FA/PA@Fe3O4 nanoparticle (smart hybrid nanocomposite, SHN) to enhance the photodynamic inactivation (PDI) of specific cancer cells. SHN coated with the PDI agent is designed to have selectivity for the folate receptor (FR) expressed on cancer cells. Structural characteristics and morphology of the fabricated MNPs were studied with X-ray diffraction and scanning electron microscopy. The photophysical properties of SHN were investigated with absorption, emission spectroscopies, and Fourier transform infrared spectroscopy. In addition, the magnetic property of Fe3O4 nanoparticle (MNP) can be utilized for the collection of SHNs by an external magnetic field. The photofunctionality was given by the photosensitizer, PA, which generates reactive oxygen species by irradiation of visible light. Generation of singlet oxygen was directly evaluated with time-resolved phosphorescence spectroscopy. Biocompatibility and cellular interaction of SHN were also analyzed by using various cancer cells, such as KB, HeLa, and MCF-7 cells which express different levels of FR on the surface. Cellular adsorption and the PDI effect of SHN on the various cancer cells in vitro were correlated well with the surface expression levels of FR, suggesting potential applicability of SHN on specific targeting and PDI of FR-positive cancers.

Study of Singlet Oxygen Dynamics on Silicon Polymer Matrix.

We report a detailed analysis of singlet oxygen generated from the photofunctional polymer film (PFPF) matrix which is the silicone polymer film (PDMS) embedded with a photosensitizer. Activation and deactivation dynamics of singlet oxygen generated from PFPFs were investigated with time-resolved phosphorescence spectroscopy. The singlet oxygen generated from PFPFs was dissipated into three different regions of the polymer matrix; the inside (component A), the surface (component B), and the outside (component C). According to the deactivation dynamics of singlet oxygen in the polymer matrix, the components B and C are expected to be more important for various applications.

Target-oriented photofunctional nanoparticles (TOPFNs) for selective photodynamic inactivation of Methicillin-resistant Staphylococcus aureus (MRSA).

To inactivate methicillin-resistant Staphylococcus aureus (MRSA) with minimum damage to host cells and tissue, target-oriented photofunctional nanoparticles (TOPFNs) were fabricated and characterized. MRSA is a predominant infective pathogen even in hospital and non-hospital environments due to its ability to develop high levels of resistance to several classes of antibiotics through various pathways. To solve this major problem, photodynamic inactivation (PDI) method applies to treat antibiotic-resistant bacteria. PDI involves the photosensitizer (PS) and light with a specific wavelength to be able to apply for a non-invasive therapeutic procedure to treat pathogenic bacteria by inducing apoptosis or necrosis of microorganisms. However, most current PDI researches have suffered from the instability of PDI agents in the biological environment due to the lack of selectivity and low solubility of PDI agents, which leads to the low PDI efficiency. In this study, the TOPFNs were fabricated by an esterification reaction to introduce hematoporphyrin (HP) and MRSA antibody to the surface of Fe3O4 nanoparticles. The TOPFNs were designed as dispersible PDI agent in biological condition, which was effectively used for selectively capturing and killing of MRSA. The capture efficiency TOPFNs was compared with PFNs as a negative control. The results showed that the capture efficiency of TOPFNs and PFNs was 95.55% and 6.43% in MRSA and L-929 cell mixed condition, respectively. And TOPFNs have a selective killing ability for MRSA with minimum damage to L-929 cells. Furthermore, PDI effect of TOPFNs was evaluated on the mice in vivo condition in order to check the possibility of practical medical application.

Fine-needle aspiration cytology of pleomorphic carcinomas of the lung.

BACKGROUND: Pleomorphic carcinoma (PC) is a rare pulmonary malignancy. Because of its rarity and histological heterogeneity, cytopathologists might suspect PC only rarely on the basis of its cytological specimen. In addition, cytological findings from fine needle aspiration (FNA) specimens have rarely been described. Hence, we investigated the cytological features of FNA in the cases of PC. METHODS: We reviewed 7 FNA specimens of PC. The patients had undergone surgical resection at the Korea Cancer Center Hospital between 2007 and 2011. The cytological features of PC were assessed and compared with the histopathological features of the corresponding surgical specimen. Immunocytochemical analysis with cytokeratin and vimentin was performed on the cell blocks. RESULTS: The tumor cells were either dispersed or arranged in loose aggregates, and generally lacked any glandular or squamous differentiation. Pleomorphic or spindle shape tumor cells were observed, and mono-, bi-, or multi-nucleated giant cells were frequently observed. The background showed necrosis and contained numerous lymphocytes and neutrophils. Immunocytochemically, the tumor cells were positive for cytokeratin and vimentin. CONCLUSIONS: PC displays characteristic cytological features. It might therefore be possible to make an accurate diagnosis of PC by assessing the degree of nuclear atypia.

Proteomic analysis of alpha-1-antitrypsin in immunoglobulin A nephropathy.

Immunoglobulin A nephropathy (IgAN) is recognized as the most common form of primary glomerulonephritis worldwide. It is characterized by mesangial cell proliferation with mesangial IgA deposition in the glomeruli, and is usually associated with secondary tubulointerstitial injury. Although significant progress has been made in the clarification of the pathogenesis of IgAN, the exact pathogenetic mechanism remains unclear. To find out the candidate proteins that play an important role in IgAN, renal cortex tissues and urine from IgAN patients were studied. The 2-DE was performed on renal tissues of IgAN and normal controls. A series of spots identified as alpha-1-antitrypsin (AAT) by mass spectrometry, were found to be significantly increased in patients with IgAN. Up-regulation of AAT variants was validated in renal cortex tissues of IgAN using Western blot and 2-DE immunoblot. Lower isoforms (˜48 kDa) and fragments (˜33 kDa), suspected as cleavage forms by proteinase attack, were especially increased in IgAN compared to normal controls. In addition, AAT proteins modified by tyrosine nitration (approximately 57 and 48 kDa), which reflects excessive oxidative stress, were increased in IgAN tissue. Additionally in the urine of IgAN, increase of AAT variants and fragments was detected by 2-DE immunoblot as well as Western blot. Immunohistochemical staining of IgAN kidney tissue revealed that the increase of AAT appeared to be derived from hypertrophic proximal tubules. The AAT staining in the glomerulus was not clear in IgAN. In addition, immunodepletion-zymography showed a positive correlation between AAT and 80-110-kDa proteinases in IgAN tissue. Further studies regarding the functional roles of AAT and the proteinases will allow better understanding of the pathogenesis of IgAN.