title: Disrupting actin filaments promotes efficient transfection of a leukemia cell line using cell adhesive protein-embedded carbonate apatite particles.
abstract: Tumor cells such as leukemia and lymphoma cells are obvious and attractive targets for gene therapy. Gene transfer and expression for cytokine and immunomodulatory molecules in various kinds of tumor cells have been shown to mediate tumor regression and antimetastatic effects. Moreover, genetically modified leukemia cells expressing costimulatory molecules or cytokines are likely to have significant therapeutic roles for patients with leukemia. One of the major hurdles to the successful implementation of these promising approaches is the lack of a suitable nanocarrier for transgene delivery and expression in a safe and effective manner. Recently, we reported on the development of a safe, efficient nanocarrier system of carbonate apatite that can assist both intracellular delivery and release of DNA, leading to very high level of transgene expression in cancer and primary cells. However, its efficiency in human lymphocytes is poor. We show here that nanocrystals of carbonate apatite, when electrostatically associated with fibronectin and/or E-cadherin-Fc, accelerated transgene delivery in a human T leukemia cell line (Jurkat). Moreover, transgene expression efficiency could be enhanced dramatically with the cell adhesive protein-embedded particles finally up to 150 times by selectively disrupting the actin filaments.
authors.affiliation: Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Midori-ku, Yokohama 226-8501, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kutsuzawa
authors.forename: S
authors.initials: S
authors.lastname: Tada
authors.forename: S
authors.initials: S
authors.lastname: Hossain
authors.forename: K
authors.initials: K
authors.lastname: Fukuda
authors.forename: K
authors.initials: K
authors.lastname: Maruyama
authors.forename: Y
authors.initials: Y
authors.lastname: Akiyama
authors.forename: T
authors.initials: T
authors.lastname: Akaike
authors.forename: E H
authors.initials: EH
authors.lastname: Chowdhury
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects*; D001031:Apatites / Q000737:chemistry*; D015820:Cadherins / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D007938:Leukemia / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry; D010957:Plasmids; D014162:Transfection / Q000379:methods*
chemical_list: D001031:Apatites; D015820:Cadherins; D015815:Cell Adhesion Molecules; D005353:Fibronectins; C030782:carboapatite