Ultrasensitive detection of SARS-CoV-2 nucleocapsid protein using large gold nanoparticle-enhanced surface plasmon resonance

The COVID-19 pandemic has created urgent demand for rapid detection of the SARS-CoV-2 coronavirus. Herein, we report highly sensitive detection of SARS-CoV-2 nucleocapsid protein (N protein) using nanoparticle-enhanced surface plasmon resonance (SPR) techniques. A crucial plasmonic role in significantly enhancing the limit of detection (LOD) is revealed for exceptionally large gold nanoparticles (AuNPs) with diameters of hundreds of nm. SPR enhanced by these large nanoparticles lowered the LOD of SARS-CoV-2 N protein to 85 fM, resulting in the highest SPR detection sensitivity ever obtained for SARS-CoV-2 N protein

HISTOLOGICAL AND IMMUNOHISTOCHEMICAL STUDIES ON THE LOCALIZATION OF IMMUNOGLOBULINS IN PORCINE PLACENTA

Porcine placentae from 18 to 114 days of gestation were investigated histologically, histochemically and immunohistochemically. The placenta was histologically divided into four areas : the chorionic fossa (CF), chorionic ridge (CR), regular areola (RA) and irregular areola (IRA). The IRA was further subdivided into fetal IRA, maternal depression and ruffled area of the maternal depression (RAMD). In histochemical analysis, a reaction product suggestive of acid mucopolysaccharides was detected exclusively in the uterine and chorionic epithelia of the IRA. In immunohistochemical analysis, the localization of IgG and IgM was demonstrated in the endometrial lamina propria mucosae, and the epithelia of the RAMD and fetal IRA. Regional IgG and IgM localization was identical to that of the acid mucopolysaccharides. In the fetal lymphatic tissues, a small number of IgG-containing cells was first noted at 114 days of gestation. In a serological survey, IgG and IgM were demonstrated at a constant level in all fetal sera from days 40 to 114 of gestation, although IgA was negative except for 2 of 23 sera from fetuses. Comparing the relative levels of maternal immunoglobulins (Igs), the fetal Igs were 1/200 in IgG and 1/500 in IgM. These results suggest that there is a possible diaplacental transition of IgG and IgM from the mother into the fetus occurring via epithelia exclusively at the RAMD and the fetal IRA

Potential of Photodynamic Therapy Based on Sugar-Conjugated Photosensitizers

In 2015, the Japanese health insurance approved the use of a second-generation photodynamic therapy (PDT) using talaporfin sodium (TS); however, its cancer cell selectivity and antitumor effects of TS PDT are not comprehensive. The Warburg effect describes the elevated rate of glycolysis in cancer cells, despite the presence of sufficient oxygen. Because cancer cells absorb considerable amounts of glucose, they are visible using positron emission tomography (PET). We developed a third-generation PDT based on the Warburg effect by synthesizing novel photosensitizers (PSs) in the form of sugar-conjugated chlorins. Glucose-conjugated (tetrafluorophenyl) chlorin (G-chlorin) PDT revealed significantly stronger antitumor effects than TS PDT and induced immunogenic cell death (ICD). ICD induced by PDT enhances cancer immunity, and a combination therapy of PDT and immune checkpoint blockers is expected to synergize antitumor effects. Mannose-conjugated (tetrafluorophenyl) chlorin (M-chlorin) PDT, which targets cancer cells and tumor-associated macrophages (TAMs), also shows strong antitumor effects. Finally, we synthesized a glucose-conjugated chlorin e6 (SC-N003HP) that showed 10,000–50,000 times stronger antitumor effects than TS (IC50) in vitro, and it was rapidly metabolized and excreted. In this review, we discuss the potential and the future of next-generation cancer cell-selective PDT and describe three types of sugar-conjugated PSs expected to be clinically developed in the future