A plasmid containing the Escherichia coli chloramphenicol acetyltransferase (CAT) gene under the control of a mammalian cAMP-regulated promoter was entrapped in H-2Kk antibody-coated liposomes composed of dioleoyl phosphatidylethanolamine, cholesterol, and oleic acid (pH-sensitive immunoliposomes). The entrapped or free DNA was injected intraperitoneally into immunodeficient (nude) BALB/c mice bearing ascites tumor generated by H-2Kk-positive RDM-4 lymphoma cells. About 20% of the injected immunoliposomes were taken up by the target RDM-4 cells. Uptake was much less when liposomes without antibody were used. The presence of the targeting antibody on liposomes also significantly decreased the nonspecific uptake of liposomes by the spleen. Significant CAT enzyme activity was detected in RDM-4 cells from mice treated with DNA entrapped in the pH-sensitive immunoliposomes. Furthermore, CAT expression in RDM-4 cells was under the control of cAMP, as only the cells from mice injected with 8-bromo-cAMP and 3-isobutyl-1-methylxanthine showed CAT activity. CAT activity in liver and spleen was much lower (by factors of 12 and 5, respectively) than in the RDM-4 cells, and the activities in these reticuloendothelial organs were not regulated by cAMP. CAT activity in RDM-4 cells from mice injected with DNA entrapped in pH-insensitive immunoliposomes (containing phosphatidylcholine in place of phosphatidylethanolamine) was approximately one-fourth that in RDM-4 cells from mice injected with pH-sensitive immunoliposomes, indicating the superior delivery efficiency of the pH-sensitive liposomes. These results are discussed in terms of the DNA-carrier potential of immunoliposomes in therapy of cancer and genetic diseases.
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http://dx.doi.org/10.1073/pnas.84.22.7851 | DOI Listing |
J Med Chem
December 2018
Dipartimento di Scienze Farmaceutiche , Università degli Studi di Milano, Via Mangiagalli 25 , I-20133 Milano , Italy.
Adenocarcinoma and glioblastoma cell lines express α7- and α9α10-containing nicotinic acetylcholine receptors (nAChRs), whose activation promotes tumor cell growth. On these cells, the triethylammoniumethyl ether of 4-stilbenol MG624, a known selective antagonist of α7 and α9α10 nAChRs, has antiproliferative activity. The structural analogy of MG624 with the mitocan RDM-4'BTPI, triphenylphosphoniumbutyl ether of pterostilbene, suggested us that molecular hybridization among their three substructures (stilbenoxy residue, alkylene linker, and terminal onium) and elongation of the alkylene linker might result in novel antitumor agents with higher potency and selectivity.
View Article and Find Full Text PDFJ Immunol
October 1994
Genetics Institute, Inc., Cambridge, MA 02140.
Peptides that are bound by the murine class I MHC molecule H-2Kk have been isolated and sequenced. The initial step in the fractionation was affinity column isolation of the peptide-class I complex from either RDM-4 or x5563 tumor cell lines. Acid denaturation of the complex followed by HPLC fractionation of the peptides allowed us to sequence individual peptides, as well as pools of peptides.
View Article and Find Full Text PDFBiol Reprod
May 1993
Department of Biology, Northeastern University, Boston, Massachusetts 02115.
Genes in the major histocompatibility complex (MHC) have been shown to play a role in development and reproduction. In the mouse, class I MHC proteins are expressed on oocytes and preimplantation embryos. Each mouse strain contains multiple class I genes located in the classical regions, K and D, and the nonclassical regions, Q and TL, of the mouse MHC, the H-2 complex.
View Article and Find Full Text PDFJ Immunol
March 1992
Department of Biochemistry, Royal Holloway and Bedford New College, University of London, Egham, Surrey, UK.
Metabolic labeling of the murine T lymphoma cell line RDM-4 with [35S] sulfate results in intense incorporation into a cell-retained component of apparent Mr approximately 100,000. This macromolecule is identified as a glycoprotein by lectin chromatography. The sulfate is not incorporated as tyrosine sulfate.
View Article and Find Full Text PDFImmunol Lett
February 1992
Department of Immunology, Tokai University School of Medicine, Isehara, Japan.
Immunization of C57BL/6 mice with syngeneic tumor cells, MBL-2, resulted in the generation of antitumor effector cells in vivo. The immunized C57BL/6 mice permanently rejected viable MBL-2 lymphoma cells, but not B16 melanoma cells. Cytotoxic T cells obtained from MBL-2-immunized mouse peritoneal cells (PEC) showed specific cytotoxicity against MBL-2, but not to YAC-1, RDM-4 and Meth A cells.
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