%0 Journal Article %1 Rothdiener2010a %A Rothdiener, Miriam %A Müller, Dafne %A Castro, Patricia Garrido %A Scholz, Anja %A Schwemmlein, Michael %A Fey, Georg %A Heidenreich, Olaf %A Kontermann, Roland E. %D 2010 %J Journal of Controlled Release %K 2010 izi kontermann %N 2 %P 251--258 %R 10.1016/j.jconrel.2010.02.020 %T Targeted delivery of SiRNA to CD33-positive tumor cells with liposomal carrier systems %U https://www.ncbi.nlm.nih.gov/pubmed/20184933 %V 144 %X SiRNA molecules represent promising therapeutic molecules, e.g. for cancer therapy. However, efficient delivery into tumor cells remains a major obstacle for treatment. Here, we describe a liposomal siRNA carrier system for targeted delivery of siRNA to CD33-positive acute myeloid leukemia cells. The siRNA is directed against the t(8;21) translocation resulting in the AML1/MTG8 fusion protein. The siRNA was encapsulated in free or polyethylene imine (PEI)-complexed form into PEGylated liposomes endowed subsequently with an anti-CD33 single-chain Fv fragment (scFv) for targeted delivery. The resulting siRNA-loaded immunoliposomes (IL) and immunolipoplexes (ILP) showed specific binding and internalization by CD33-expressing myeloid leukemia cell lines (SKNO-1, Kasumi-1). Targeted delivery of AML1/MTG8 siRNA, but not of mismatch control siRNA, reduced AML1/MTG8 mRNA and protein levels and decreased leukemic clonogenicity, a hallmark of leukemic self-renewal. Although this study revealed that further modifications are necessary to increase efficacy of siRNA delivery and silencing, we were able to establish a targeted liposomal siRNA delivery system combining recombinant antibody fragments for targeted delivery with tumor cell-specific siRNA molecules as therapeutic agents. © 2010 Elsevier B.V. %7 2010/02/27 %@ 1873-4995 (Electronic)$\backslash$r0168-3659 (Linking)

@article{Rothdiener2010a, abstract = {SiRNA molecules represent promising therapeutic molecules, e.g. for cancer therapy. However, efficient delivery into tumor cells remains a major obstacle for treatment. Here, we describe a liposomal siRNA carrier system for targeted delivery of siRNA to CD33-positive acute myeloid leukemia cells. The siRNA is directed against the t(8;21) translocation resulting in the AML1/MTG8 fusion protein. The siRNA was encapsulated in free or polyethylene imine (PEI)-complexed form into PEGylated liposomes endowed subsequently with an anti-CD33 single-chain Fv fragment (scFv) for targeted delivery. The resulting siRNA-loaded immunoliposomes (IL) and immunolipoplexes (ILP) showed specific binding and internalization by CD33-expressing myeloid leukemia cell lines (SKNO-1, Kasumi-1). Targeted delivery of AML1/MTG8 siRNA, but not of mismatch control siRNA, reduced AML1/MTG8 mRNA and protein levels and decreased leukemic clonogenicity, a hallmark of leukemic self-renewal. Although this study revealed that further modifications are necessary to increase efficacy of siRNA delivery and silencing, we were able to establish a targeted liposomal siRNA delivery system combining recombinant antibody fragments for targeted delivery with tumor cell-specific siRNA molecules as therapeutic agents. {\textcopyright} 2010 Elsevier B.V.}, added-at = {2018-02-01T15:53:50.000+0100}, author = {Rothdiener, Miriam and M{\"{u}}ller, Dafne and Castro, Patricia Garrido and Scholz, Anja and Schwemmlein, Michael and Fey, Georg and Heidenreich, Olaf and Kontermann, Roland E.}, biburl = {https://puma.ub.uni-stuttgart.de/bibtex/24c50e70e1128dcf8a69270cf6a912785/cristiano}, doi = {10.1016/j.jconrel.2010.02.020}, edition = {2010/02/27}, interhash = {97d512ec564e0cca61ac915c30730ddb}, intrahash = {4c50e70e1128dcf8a69270cf6a912785}, isbn = {1873-4995 (Electronic)$\backslash$r0168-3659 (Linking)}, issn = {01683659}, journal = {Journal of Controlled Release}, keywords = {2010 izi kontermann}, number = 2, pages = {251--258}, pmid = {20184933}, timestamp = {2018-07-25T12:32:30.000+0200}, title = {{Targeted delivery of SiRNA to CD33-positive tumor cells with liposomal carrier systems}}, url = {https://www.ncbi.nlm.nih.gov/pubmed/20184933}, volume = 144, year = 2010 }