| 研究実績の概要 |
The aim for this year was to evaluate the targeting potencies of the synthesized delivery system for siRNAs and to consider further modification of the system based on the cell-assay results. As a promising delivery system, antibody-PAMAM conjugate were designed and synthesized last year. Considering the high loading capacity and cytotoxicity, generation-5 (G5) PAMAM was selected as a preliminary trial. This year, generation-4 (G4) PAMAM was also considered in order to reduce the molecular weight and the possibility of cytotoxicity due to polycationic nature of the nanomolecule, and to compare the results with that from G5-PAMAM. The surface of the PAMAM was decorated with various components, such as conjugation moiety, fluorescent moiety, and masking groups. As a smart targeting moeity single chain (scFV) antibody fragment was considered and obtained from the laboratory of biomolecular science, Hokkaido university. Apart from these, the research concern of this year was to synthesize homogeneous bioconjugates containing fixed number of dendrimer vs antibody moiety. The ability to estimate the number of dendrimer with respect to antibody is expected to allow controlling the number of siRNA payload that would limit the possible cytotoxicity of the nanoparticle. Preliminary cell-assay data has been obtained that indicated a possibility of aggregation of the nanoparticles and lesser potency. To address the concern of aggregation and site-specificity of the nanoparticle, further considerations to modify the surface of the dendrimers and conjugation methods are required.
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