Leukemia-specific siRNA delivery by immunonanoplexes consisting of anti-JL1 minibody conjugated to oligo-9 Arg-peptides
| Autor: | Hyung Geun Song, Sang Il Park, Jung Seok Kim, Hwa Yeon Jeong, Yong Serk Park, Kyeong Cheon Jung, Jin Ee Baek, Yeon Kyung Lee, Keun Sik Kim, Sang Soon Yoon |
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| Rok vydání: | 2010 |
| Předmět: |
Antigens
Differentiation T-Lymphocyte Small interfering RNA Leukemia T-Cell Recombinant Fusion Proteins Mice SCID Protein Engineering Jurkat cells Jurkat Cells Mice Antigen medicine Animals Humans RNA Small Interfering Molecular Biology Microscopy Confocal biology Antibodies Monoclonal RNA Genetic Therapy Cell Biology General Medicine medicine.disease Molecular biology Peptide Fragments Leukemia medicine.anatomical_structure Cancer cell biology.protein Female Bone marrow Antibody Neoplasm Transplantation |
| Zdroj: | Molecules and Cells. 29:457-462 |
| ISSN: | 0219-1032 1016-8478 |
| DOI: | 10.1007/s10059-010-0056-5 |
| Popis: | Targeted mRNA degradation by short interfering RNAs (siRNAs) offers a great potential to treat cancers. siRNA therapeutics for leukemias are, however, hindered by poor intracellular uptake, limited blood stability and nonspecific delivery. To solve these problems, we developed an anti-JL1 immunonanoplex (antibody-coupled nanocomplex) for siRNA delivery using anti-JL1 minibody (leukemia cell-specific minibody) conjugated to oligo-9-Arg peptide (9R) for effective siRNA delivery to leukemic cells. The anti-JL1 immunonanoplexes were able to deliver siRNA specifically to leukemic cells (CEM and Jurkat), but not to control cancer cells (H9). According to FACS and confocal microscopic analysis, siRNAs delivered by immunonanoplex particles were rapidly taken up by the JL1-positive cancer cells in 2 h. Furthermore, we showed that the anti-JL1 immunonanoplexes were effectively targeted to JL1-positive cells (CEM) inoculated in the mouse bone marrow. These results suggest that the anti-JL1 immunonanoplex is a powerful siRNA delivery system for human leukemia therapies. |
| Databáze: | OpenAIRE |
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