ABSTRACT
Lipid nanoparticle (LNP)-based drug delivery systems have become the most clinically advanced non-viral delivery technology. LNPs can encapsulate and deliver a wide variety of bioactive agents, including the small molecule drugs, proteins and peptides, and nucleic acids. However, as the physicochemical properties of small- and macromolecular cargos can vary drastically, every LNP carrier system needs to be carefully tailored in order to deliver the cargo molecules in a safe and efficient manner. Our group applied the combinatorial library synthesis approach and in vitro and in vivo screening strategy for the development of LNP delivery systems for drug delivery. In this Review, we highlight our recent progress in the design, synthesis, characterization, evaluation, and optimization of combinatorial LNPs with novel structures and properties for the delivery of small- and macromolecular therapeutics both in vitro and in vivo. These delivery systems have enormous potentials for cancer therapy, antimicrobial applications, gene silencing, genome editing, and more. We also discuss the key challenges to the mechanistic study and clinical translation of new LNP-enabled therapeutics.
ABSTRACT
<p><b>OBJECTIVES</b>To study the interaction of beta-2-glycoprotein I (beta 2GPI) with the membrane of hepatocytes and determine whether beta 2GPI participates in HBV infection.</p><p><b>METHODS</b>Ligand blotting, fluorescence microscopy, and fluorescence activated cell sorter (FACS) analysis were used to detect the specific interaction of beta 2GPI with the hepatoma cell line smmc7721, the gastric carcinoma cell line SGC7901, and the lymphoma cell line HL-60.</p><p><b>RESULTS</b>A specific 40 kDa beta 2GPI band was observed by ligand blotting in the case of smmc7721 cells. No such band was observed in SGC7901 or HL-60 cells. Fluorescence microscopy also revealed specific binding of FITC-beta 2GPI to smmc7721 cells, but neither to SGC7901 nor HL-60 cells. FACS analysis demonstrated that the binding rate of FITC-beta 2GPI to smmc7721 cells was significantly higher than these in SGC7901 and HL-60 cells (P < 0.01). The binding rate to smmc7721 cells did not increase with increasing amounts of FITC-beta 2GPI.</p><p><b>CONCLUSIONS</b>There is a specific beta 2GPI-binding protein on the membrane of hepatoma cells in cell line smmc7721 which as the beta 2GPI receptor may participate in HBV infection of hepatocytes.</p>
Subject(s)
Animals , Carcinoma, Hepatocellular , Cell Membrane , Metabolism , Flow Cytometry , Glycoproteins , Metabolism , Hepatocytes , Metabolism , Liver Neoplasms, Experimental , Metabolism , Platelet Glycoprotein GPIb-IX Complex , Platelet Membrane Glycoproteins , Tumor Cells, Cultured , beta 2-Glycoprotein IABSTRACT
<p><b>OBJECTIVE</b>To clarify the binding character between Beta-2-glycoprotein I (Beta-2-GPI) and HBsAg.</p><p><b>METHODS</b>Beta-2-GPI was purified from human plasma and labelled with biotin. Solid phase enzyme linked absorbance assay was used to investigate its binding with HBsAg.</p><p><b>RESULTS</b>Biotinylated Beta-2-GPI was found to bind HBsAg and the reaction could be inhibited by excess unlabelled Beta-2-GPI.</p><p><b>CONCLUSIONS</b>Beta-2-GPI may play a role in hepatitis B virus infection.</p>
Subject(s)
Humans , Binding Sites , Biotinylation , Enzyme-Linked Immunosorbent Assay , Methods , Glycoproteins , Metabolism , Hepatitis B Surface Antigens , Metabolism , Hepatitis B virus , Chemistry , Metabolism , beta 2-Glycoprotein IABSTRACT
Objective:To investigate oxidative modification of β2-glycoprotein Ⅰ in vit ro.Methods:Rat β2-glycoprotein Ⅰ was purified and characterized,then oxidize d by hypoxanthine plus xanthine oxidase as a supreroxide free radical generating system;carbonl groups of β2-glycoprotein Ⅰ were detected by the reaction w ith 2,4-dinitrophenylhudrazine.Results:There was a significant increase of carbonyl groups formation in β2- glycoprotein Ⅰ oxidized in comparison with native β2-glycoprotein Ⅰ (P <0.05). Conclusion:Carbonyl groups have been formed in vitro on rat β2-glycoprotein Ⅰ after oxidative modification using hypoxanthine plus xanthine oxidase system.
ABSTRACT
Abstract-Eleven mouse monoclonal antibodies (McAbS)specific for human alpha-fetopr-otein(AFP) have been produced by the hybridoma technique. Immunodiffusion was us-ed for determining the immunoglobulin class and subclass of the McAbS. Seven of them are IgG; two are IgM. At least 4 different antigenic determinants on human AFPcan be recognized by using the McAbS and cross-two-site sandwich solid radioimmun-oassay. One of the McAbS can specially react with one of the fragments of AFP dig-ested by pepsin. In addition, the cross-reactivity among the AFPs of different mam-malian species was also tested by using the McAbS.