MDPIActa Medica Okayama2075-17291122021A Novel 89Zr-labeled DDS Device Utilizing Human IgG Variant (scFv): gLactosomeh Nanoparticle-Based Theranostics for PET Imaging and Targeted Therapy158ENMelissa Siaw HanLimDepartment of Cell Chemistry, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityTakashiOhtsukiDepartment of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityFumiakiTakenakaCollaborative Research Centre for OMIC, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityKazukoKobayashiCollaborative Research Centre for OMIC, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityMasaruAkehiCollaborative Research Centre for OMIC, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityHirotakaUjiDepartment of Material Chemistry, Graduate School of Engineering, Kyoto UniversityHirotsuguKobuchiDepartment of Cell Chemistry, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityTakanoriSasakiCollaborative Research Centre for OMIC, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityEiichiOzekiTechnology Research Laboratory, Shimadzu CorporationEijiMatsuuraDepartment of Cell Chemistry, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversitygTheranostics,h a new concept of medical advances featuring a fusion of therapeutic and diagnostic systems, provides promising prospects in personalized medicine, especially cancer. The theranostics system comprises a novel 89Zr-labeled drug delivery system (DDS), derived from the novel biodegradable polymeric micelle, gLactosomeh nanoparticles conjugated with specific shortened IgG variant, and aims to successfully deliver therapeutically effective molecules, such as the apoptosis-inducing small interfering RNA (siRNA) intracellularly while offering simultaneous tumor visualization via PET imaging. A 27 kDa-human single chain variable fragment (scFv) of IgG to establish clinically applicable PET imaging and theranostics in cancer medicine was fabricated to target mesothelin (MSLN), a 40 kDa-differentiation-related cell surface glycoprotein antigen, which is frequently and highly expressed by malignant tumors. This system coupled with the cell penetrating peptide (CPP)-modified and photosensitizer (e.g., 5, 10, 15, 20-tetrakis (4-aminophenyl) porphyrin (TPP))-loaded Lactosome particles for photochemical internalized (PCI) driven intracellular siRNA delivery and the combination of 5-aminolevulinic acid (ALA) photodynamic therapy (PDT) offers a promising nano-theranostic-based cancer therapy via its targeted apoptosis-inducing feature. This review focuses on the combined advances in nanotechnology and material sciences utilizing the g89Zr-labeled CPP and TPP-loaded Lactosome particlesh and future directions based on important milestones and recent developments in this platform. No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2405-8440662020Rapid and specific detection of oxidized LDL/2GPI complexes via facile lateral flow immunoassaye04114ENXian WenTanDepartment of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesFumiakiTakenakaCollaborative Research Center (OMIC), Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHironoriTakekawaFaculty of Medicine, Okayama UniversityEijiMatsuuraDepartment of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences2-Glycoprotein I (2GPI) forms indissociable complex with oxidized LDL (oxLDL) into proatherogenic oxLDL/2GPI complex through a specific ligand known as 7-ketocholesteryl-9-carboxynonanoate (oxLig-1). Recent discoveries have demonstrated the atherogenicity of these complexes in patients of both systemic and non-systemic autoimmune diseases. Hence, serological level of oxLDL/2GPI complexes may represent one crucial clinical parameter for disease prognosis of atherosclerosis-related diseases. Herein, we established a simple, specific and rapid gold nanoparticle (GNP) based lateral flow immunoassay (LFIA) to quantify oxLDL/2GPI complexes from test samples. Specificities of hybridoma cell-derived monoclonal antibodies against antigen, optimal conditions for conjugation of antibody with GNP, and sensitivity of oxLDL/2GPI LFIA in comparison to an ELISA-based detection method were assessed accordingly. The established oxLDL/2GPI LFIA was capable of detecting oxLDL/2GPI specifically without interference from autoantibodies and solitary components of oxLDL/2GPI present in test samples. A significant correlation (R2 > 0.8) was also obtained with the oxLDL/2GPI LFIA when compared to the ELISA-based detection. On the whole, the oxLDL/2GPI LFIA remains advantageous over the oxLDL/2GPI ELISA. The unnecessary washing step, short developmental and analytical time support facile and rapid detection of oxLDL/2GPI as opposed to the laborious ELISA system.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7012016The Function of 2-glycoprotein I in Angiogenesis and Its in Vivo Distribution in Tumor Xenografts1324ENArum Tri WahyuningsihLianhuaShenKazukoKobayashiTakanoriSasakiFumiakiTakenakaTakahisaHanadaMasaruAkehiAkiyaAkahoshiEiichiOzekiEijiAndoEijiMatsuuraOriginal Article10.18926/AMO/53999Intact 2-glycoprotein I (i2GPI) is a glycoprotein that regulates coagulation and fibrinolysis. Nicked 2GPI (n2GPI) possesses an angiogenic property at a relatively low concentration, and an antiangiogenic property at a high concentration. Here we investigated the functions of i 2GPI and n2GPI in vascular endothelial growth factor (VEGF)-A-induced endothelial cell proliferation and tube formation. We used noninvasive PET imaging to analyze the in vivo distribution of intravenously injected 2GPI variants in tumor lesions in mice. i2GPI was incubated with plasmin to obtain n2GPI, and its N-terminal sequence was analyzed. n2GPI had at least one other cleavage site upstream of the 2GPIʼs domain V, whereas the former plasmin-cleavage site locates between K317 and T318. Both of intact and nicked 2GPI significantly inhibited the VEGF-A-induced cell proliferation and the tube formation of human umbilical vein endothelial cells (HUVECs). PET imaging visualized considerably distributed intensities of all tested 2GPI variants in tumor lesions of pancreatic tumor cell-xenografts. These results indicate that 2GPI may be physiologically and pathophysiologically important in the regulation of not only coagulation and fibrinolysis, but also angiogenesis.No potential conflict of interest relevant to this article was reported.