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Cell membrane-derived vesicles for delivery of therapeutic agents

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Acta Pharmaceutica Sinica B 2021年第8期11卷 2096-2113页

作者： Quoc-Viet Le Jaiwoo Lee Hobin Lee gayong shim Yu-Kyoung Oh College of Pharmacy and Research Institute of Pharmaceutical Sciences Seoul National UniversitySeoul 08826Republic of Korea School of Systems Biomedical Science Soongsil UniversitySeoul 06978Republic of Korea

Cell membranes have recently emerged as a new source of materials for molecular delivery *** membranes have been extruded or sonicated to make nanoscale *** synthetic lipid or polymeric nanoparticles,cell membrane-derived vesicles have a unique multicomponent feature,comprising lipids,proteins,and *** cell membrane-derived vesicles contain the intrinsic functionalities and signaling networks of their parent cells,they can overcome various obstacles encountered in ***,the different natural combinations of membranes from various cell sources expand the range of cell membrane-derived vesicles,creating an entirely new category of drug-delivery *** membrane-derived vesicles can carry therapeutic agents within their interior or can coat the surfaces of drug-loaded core *** membranes typically come from single cell sources,including red blood cells,platelets,immune cells,stem cells,and cancer ***,recent studies have reported hybrid sources from two different types of *** review will summarize approaches for manufacturing cell membrane-derived vesicles and treatment applications of various types of cell membrane-derived drug-delivery systems,and discuss challenges and future directions.

关键词： Cell membrane-derived vesicles Membrane engineering Drug-delivery systems Blood cells Immune cells Stem cells Cancer cells Manufacturing

Molecular engineering of antibodies for site-specific conjugation to lipid polydopamine hybrid nanoparticles

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Acta Pharmaceutica Sinica B 2020年第11期10卷 2212-2226页

作者： Hobin Yang Quoc-Viet Le gayong shim Yu-Kyoung Oh Young Kee Shin Laboratory of Molecular Pathology and Cancer Genomics College of Pharmacy and Research Institute of Pharmaceutical SciencesSeoul National UniversitySeoul 08826Republic of Korea College of Pharmacy and Research Institute of Pharmaceutical Sciences Seoul National UniversitySeoul 08826Republic of Korea Bio-MAX Seoul National UniversitySeoul 08826Republic of Korea

Conjugation of antibodies to nanoparticles allows specific cancer targeting,but conventional conjugation methods generate heterogeneous conjugations that cannot guarantee the optimal orientation and functionality of the conjugated ***,a molecular engineering technique was used for sitespecific conjugation of antibodies to *** designed an anti-claudin 3(CLDN3)antibody containing a single cysteine residue,h4 G3 cys,then linked it to the maleimide group of lipid polydopamine hybrid nanoparticles(LPNs).Because of their negatively charged lipid coating,LPNs showed high colloidal stability and provided a functional surface for site-specific conjugation of h4 G3 *** activity of h4 G3 cys was tested by measuring the binding of h4 G3 cys-conjugated LPNs(C-LPNs)to CLDN3-positive tumor cells and assessing its subsequent photothermal effects.C-LPNsspecifically recognized CLDN3-overexpressing T47 D breast cancer cells but not CLDN3-negative Hs578 T breast cancer *** binding of C-LPNs to CLDN3-overexpressing T47 D cells resulted in significantly higher temperature generation upon NIR irradiation and potent anticancer photothermal *** with this,intravenous injection of C-LPNsin a T47 D xenograft mouse model followed by NIR irradiation caused remarkable tumor ablation compared with other treatments through high temperature *** results establish an accurate antibody-linking method and demonstrate the possibility of developing therapeutics using antibody-guided nanoparticles.

关键词： Molecular engineering Site-specific conjugation Lipid polydopamine hybrid nanoparticles Claudin 3 Photothermal therapy

DNA-based artificial dendritic cells for in situ cytotoxic T cell stimulation and immunotherapy

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Bioactive Materials 2022年第9期7卷 160-172页

作者： Quoc-Viet Le Jaiwoo Lee Junho Byun gayong shim Yu-Kyoung Oh College of Pharmacy and Research Institute of Pharmaceutical Sciences Seoul National University1 Gwanak-roGwanak-guSeoul08826Republic of Korea School of Systems Biomedical Science Soongsil UniversitySeoul06978Republic of Korea

In immunotherapy,ex vivo stimulation of T cells requires significant resources and ***,we report artificial dendritic cell-mimicking DNA microflowers(DM)for programming T cell stimulation in *** mimic dendritic cells,DNA-based artificial dendritic microflowers were constructed,surface-coated with polydopamine,and further modified with anti-CD3 and anti-CD28 antibodies to yield antibody-modified DM(DM-A).The porous structure of DM-A allowed entrapment of the T cell-stimulating cytokine,ineterleukin-2,yielding interleukin-2-loaded DM-A(DM-AI).For comparison,polystyrene microparticles coated with polydopamine and modified with anti-CD3 and anti-CD28 antibodies(PS-A)were *** to PS-A,DM-AI showed significantly greater contact with T cell ***-AI provided the highest ex vivo expansion of cytotoxic T *** injection of DM-AI to tumor tissues induced the recruitment of T cells and expansion of cytotoxic T cells in tumor *** the other groups,model animals injected with DM-AI did not exhibit growth of primary *** of mice with DM-AI also protected against growth of a rechallenged distant tumor,and thus prevented tumor recurrence in this ***-AI has great potential for programmed stimulation of CD8+T *** concept could be broadly extended for the programming of specific T cell stimulation profiles.

关键词： Artificial dendritic cell DNA microflower In situ T cell stimulation Programmed T cell expansion Immunotherapy

Surface-modified liposomes for syndecan 2-targeted delivery of edelfosine

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Asian Journal of Pharmaceutical Sciences 2016年第5期11卷 596-602页

作者： gayong shim Yong Hee Yu Soondong Lee Jinyoung Kim Yu-Kyoung Oh College of Pharmacy and Research Institute of Pharmaceutical Sciences Seoul National University

Here, we report that the modification of liposome surfaces with AG73 peptides enhances delivery of the lipophilic anticancer drug, edelfosine, to tumor cells overexpressing the cellsurface receptor, syndecan 2. To test the effect of liposomal surface density of AG73 peptides on cellular uptake, we synthesized AG73 peptide-conjugated polyethylene glycol(MW 2000)lipid and incorporated it into fluorescence dye-labeled anionic liposomes with different ligand densities(1, 2, or 5 mol% of total lipids). Cellular uptake of AG73-peptide–modified liposomes gradually increased in proportion to the surface ligand density. The percentages of cells positive for AG73-modified, fluorescent-dye–labeled liposomes were 19.8 ± 2.0%, 23.1 ± 5.0%,and 99.2 ± 1.0%, for ligand mole percentages of 1, 2, and 5, respectively. The cell-targeting ability of AG73-modified liposomes was not significantly altered by the serum content of culture media. In keeping with the observed enhanced cellular uptake, AG73-peptide–modified liposomes entrapping edelfosine exhibited greater cancer cell-killing effects compared with unmodified liposomes. Following intravenous administration into tumor-bearing mice,AG73-peptide–modified liposomes showed 2.1-fold greater accumulation in tumors than unmodified liposomes. These results support the feasibility of using syndecan 2–directed liposomes for delivery of edelfosine.

关键词： Ligand density AG73 peptide Syndecan 2 Liposome Anticancer drug Edelfosine

Application of cationic liposomes for delivery of nucleic acids

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Asian Journal of Pharmaceutical Sciences 2013年第2期8卷 72-80页

作者： gayong shim Mi-Gyeong Kim Joo Yeon Park Yu-Kyoung Oh College of Pharmacy Seoul National UniversityDaehak-dongSeoul 151-742South Korea

Nucleic acid-based bioactive substances have recently emerged as a new class of nextgeneration therapeutics, but their development has been limited by their relatively weakdelivery into target cells. Cationic liposomes have been studied as a means to enhance thestability of nucleic acid therapeutics in the bloodstream and improve their cellular *** nucleic acid therapeutics, siRNA and plasmid DNA have been extensively tested fordelivery using cationic liposomes. This review discusses recent progress in the applicationof cationic liposomes for the delivery of nucleic acid therapeutics.

关键词： Cationic lipid Liposomes Delivery Nucleic acid therapeutics siRNA Plasmid DNA

Nanotechnology and vaccine development

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Asian Journal of Pharmaceutical Sciences 2014年第5期9卷 227-235页

作者： Mi-Gyeong Kim Joo Yeon Park Yuna Shon Gunwoo Kim gayong shim Yu-Kyoung Oh College of Pharmacy and Research Institute of Pharmaceutical Sciences Seoul National UniversitySeoul 151-742Republic of Korea Department of Molecular Medicine and Biopharmaceutical Sciences Graduate School of Convergence ScienceSeoul National UniversityDaehak-dongGwanank-guSeoulRepublic of Korea

Despite the progress of conventional vaccines,improvements are clearly required due to concerns about the weak immunogenicity of these vaccines,intrinsic instability in vivo,toxicity,and the need for multiple *** overcome such problems,nanotechnology platforms have recently been incorporated into vaccine ***-based delivery systems offer an opportunity to enhance the humoral and cellular immune *** advantage is attributable to the nanoscale particle size,which facilitates uptake by phagocytic cells,the gut-associated lymphoid tissue,and the mucosa-associated lymphoid tissue,leading to efficient antigen recognition and *** the surfaces of nanocarriers with a variety of targeting moieties permits the delivery of antigens to specific cell surface receptors,thereby stimulating specific and selective immune *** this review,we introduce recent advances in nanocarrierbased vaccine delivery systems,with a focus on the types of carriers,including liposomes,emulsions,polymer-based particles,and carbon-based *** describe the remaining challenges and possible breakthroughs,including the development of needlefree nanotechnologies and a fundamental understanding of the in vivo behavior and stability of the nanocarriers in nanotechnology-based delivery systems.

关键词： Nanotechnology Vaccine delivery Liposomes Emulsions Polymeric nanocarriers Carbon nanomaterials