Expression of chemokine genes in macrophages and endothelial cells infected with Orientia tsutsugamushi Orientia tsutsugamushi 감염에 의한 대식세포주와 혈관내피세포에서의 chemokine 발현양상 분석

Thesis (doctoral)--서울대학교 대학원 :의학과 미생물학전공,2001.Docto

Application of ZnO-based nanocomposites for vaccines and cancer immunotherapy

Engineering and application of nanomaterials have recently helped advance various biomedical fields. Zinc oxide (ZnO)-based nanocomposites have become one of the most promising candidates for biomedical applications due to their biocompatibility, unique physicochemical properties, and cost-effective mass production. In addition, recent advances in nano-engineering technologies enable the generation of ZnO nanocomposites with unique three-dimensional structures and surface characteristics that are optimally designed for in vivo applications. Here, we review recent advances in the application of diverse ZnO nanocomposites, with an especial focus on their development as vaccine adjuvant and cancer immunotherapeutics, as well as their intrinsic properties interacting with the immune system and potential toxic effect in vivo. Finally, we summarize promising proof-of-concept applications as prophylactic and therapeutic vaccines against infections and cancers. Understanding the nano-bio interfaces between ZnO-based nanocomposites and the immune system, together with bio-effective design of the nanomaterial using nano-architectonic technology, may open new avenues in expanding the biomedical application of ZnO nanocomposites as a novel vaccine platform.OAIID:RECH_ACHV_DSTSH_NO:T201915554RECH_ACHV_FG:RR00200001ADJUST_YN:EMP_ID:A079480CITE_RATE:4.773FILENAME:2019 Pharmaceutics 2019_SEP.pdfDEPT_NM:의과학과EMAIL:[email protected]_YN:YFILEURL:https://srnd.snu.ac.kr/eXrepEIR/fws/file/63eb664a-ddd6-491b-9262-e082d1535b66/linkY

Application of ZnO-Based Nanocomposites for Vaccines and Cancer Immunotherapy

Engineering and application of nanomaterials have recently helped advance various biomedical fields. Zinc oxide (ZnO)-based nanocomposites have become one of the most promising candidates for biomedical applications due to their biocompatibility, unique physicochemical properties, and cost-effective mass production. In addition, recent advances in nano-engineering technologies enable the generation of ZnO nanocomposites with unique three-dimensional structures and surface characteristics that are optimally designed for in vivo applications. Here, we review recent advances in the application of diverse ZnO nanocomposites, with an especial focus on their development as vaccine adjuvant and cancer immunotherapeutics, as well as their intrinsic properties interacting with the immune system and potential toxic effect in vivo. Finally, we summarize promising proof-of-concept applications as prophylactic and therapeutic vaccines against infections and cancers. Understanding the nano-bio interfaces between ZnO-based nanocomposites and the immune system, together with bio-effective design of the nanomaterial using nano-architectonic technology, may open new avenues in expanding the biomedical application of ZnO nanocomposites as a novel vaccine platform

Immunization with a recombinant antigen composed of conserved blocks from TSA56 provides broad genotype protection against scrub typhus

Scrub typhus is an acute febrile disease caused by Orientia tsutsugamushi infection. Despite the wide range of approaches explored during the last seventy years, an effective prophylactic vaccine is not yet available. Here, we developed a novel recombinant antigen derived from conserved regions of 56kDa type-specific antigen (TSA56), a major outer membrane protein responsible for genetic heterogeneity and antigenicity, and evaluated it as a protective vaccine antigen. Our findings demonstrate that immunization with conserved blocks of TSA56 (cTSA56) not only provides protective immunity against lethal challenges with the homologous genotype, but also confers significantly better protection against heterologous genotypes than TSA56. Adoptive transfer of CD4(+) or CD8(+) T cells from immunized mice provided significantly enhanced protection against lethal challenge, whereas immune B cells failed to do so, indicating that cellular immunity against the conserved epitopes plays a protective role. Moreover, immunization with a 10-mer peptide mixture, screened from CD8(+) T cell epitopes within the conserved region of TSA56, provided enhanced protection against lethal challenge with O. tsutsugamushi. Therefore, this novel recombinant antigen is a promising candidate for scrub typhus vaccine against a wide range of O. tsutsugamushi genotypes.OAIID:RECH_ACHV_DSTSH_NO:T201915551RECH_ACHV_FG:RR00200001ADJUST_YN:EMP_ID:A079480CITE_RATE:6.032DEPT_NM:의과학과EMAIL:[email protected]_YN:YY

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.OAIID:RECH_ACHV_DSTSH_NO:T201915553RECH_ACHV_FG:RR00200001ADJUST_YN:EMP_ID:A079480CITE_RATE:2.923DEPT_NM:의과학과EMAIL:[email protected]_YN:YN

Application of radially grown ZnO nanowires on poly-l-lactide microfibers complexed with a tumor antigen for cancer immunotherapy

Zinc oxide (ZnO)-based nanocomposites have shown promising potential for various biomedical applications, including vaccine development, owing to their multifunctionality and biocompatibility. Here, we synthesized radially grown ZnO nanowires (NWs) on poly-l-lactic acid (PLLA) microfibers with unique 3-dimensional structure and applied them as therapeutic cancer vaccines. This inorganic-organic hybrid nanocomposite has mild cellular toxicity but efficiently delivers a tumor antigen into dendritic cells, cellular bridges between innate and adaptive immunity, to stimulate them to express inflammatory cytokines and activation surface markers. We also demonstrated that the hybrid nanocomposites successfully induce tumor antigen-specific cellular immunity and significantly inhibit tumor growth in vivo. ZnO NWs on PLLA fibers systemically reduced immune suppressive T-Reg cells and enhanced the infiltration of T cells into tumor tissues, compared to mice immunized with PLLA fibers coated with the antigen. Our current findings open a new avenue in extending the biomedical application of inorganic metal oxide-inert organic hybrid nanocomposites as a novel vaccine platform.OAIID:RECH_ACHV_DSTSH_NO:T201915549RECH_ACHV_FG:RR00200001ADJUST_YN:EMP_ID:A079480CITE_RATE:7.233DEPT_NM:의과학과EMAIL:[email protected]_YN:YY

Severe fever with thrombocytopenia syndrome virus infection or mixed infection with scrub typhus in South Korea in 2000-2003

Severe fever with thrombocytopenia syndrome is a tick-borne viral disease, with a high mortality rate that was first reported in China in 2009. Scrub typhus is an acute febrile illness caused by Orientia tsutsugamushi, a bacterium transmitted to humans through chigger mite bites. Severe fever with thrombocytopenia syndrome and scrub typhus are endemic to South Korea. To investigate evidence of severe fever with thrombocytopenia syndrome virus (SFTSV) infection or mixed infection with scrub typhus in South Korea, we examined 2,329 sera samples collected from patients presenting from November 1, 2000, to November 1, 2003, for the diagnosis of rickettisal diseases at Seoul National University, Seoul, South Korea. We found retrospective evidence of SFTSV infection or mixed infection with scrub typhus in South Korea in 2000-2003. Severe fever with thrombocytopenia syndrome virus infections in South Korea occurred before previously reported cases and were more concurrent with those in China. It is important to consider SFTSV infection in patients with scrub typhus.OAIID:RECH_ACHV_DSTSH_NO:T201915555RECH_ACHV_FG:RR00200001ADJUST_YN:EMP_ID:A079480CITE_RATE:2.315FILENAME:2019 AJMH 2019_SEP.pdfDEPT_NM:의과학과EMAIL:[email protected]_YN:YFILEURL:https://srnd.snu.ac.kr/eXrepEIR/fws/file/d6a4419a-8754-4177-a4c1-4e0670473a2d/linkY