A nonviral carrier for targeted gene delivery to tumor cells

Department of PLG/Medical Biology, Academic Hospital Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands.
Cancer Gene Therapy (Impact Factor: 2.42). 03/2004; 11(2):156-64. DOI: 10.1038/sj.cgt.7700668
Source: PubMed


In this study, we developed a nonviral, cationic, targeted DNA-carrier system by coupling SAINT/DOPE lipids to monoclonal antibodies. The two monoclonal antibodies used were both tumor specific, that is, MOC31 recognizes the epithelial glycoprotein EGP-2 present in carcinomas and Herceptin recognizes the HER-2/neu protein in breast and ovarian cancers. Coupling was performed under nonreducing conditions by covalent attachment. The coupling procedure appeared to be reproducible and the binding capacity of the antibody was not affected by linking them to the cationic lipid. Binding and transfection efficiency was assayed with target cells and nontarget cells. SAINT/DOPE lipoplexes as such appeared to be an effective transfection reagent for various cell lines. After coupling SAINT/DOPE to the monoclonal antibodies or F(ab)2 fragments, it was shown that the targeted MoAb-SAINT/DOPE lipoplexes preferably bound to target cells, compared to binding to the nontarget cells, especially for the Herceptin-SAINT/DOPE lipoplexes. More importantly, transfection of the target cells could also be improved with these targeted lipoplexes. In conclusion, we have shown that by using monoclonal antibody-coupled SAINT/DOPE lipoplexes cells targeted gene delivery can be achieved, and also a higher number of transfected target cells was seen.

Download full-text


Available from: Lou F.M.H. de Leij, Nov 21, 2014
  • Source
    • "Introduction of nanotechnology and the development of nano-carrier-based vaccines have started to receive a lot of attention in order to provide effective immunization through better targeting and triggering antibody response at the cellular level. Many studies demonstrated that, non-viral carrier systems are widely used as transfection agents to deliver nucleic acids for both in vitro and in vivo applications [26] [27]. Recently, a few nanoparticle-based vaccines have shown to be effective in the induction of immune responses in animal models without the need for an adjuvant [28]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: An important aspect in optimizing DNA vaccination is antigen delivery to the site of action. In this way, any alternative delivery system having higher transfection efficiency and eventual superior antibody production needs to be further explored. The novel nanoparticle, pDNA/PEI/γ-PGA complex, is one of a promising delivery system, which is taken up by cells and is shown to have high transfection efficiency. The immunostimulatory effect of this novel nanoparticle (NP) coated plasmid encoding Plasmodium yoelii MSP1-C-terminus was examined. Groups of C57BL/6 mice were immunized either with NP-coated MSP-1 plasmid, naked plasmid or NP-coated blank plasmid, by three different routes of administration; intravenous (i.v.), intraperitoneal (i.p.) and subcutaneous (s.c). Mice were primed and boosted twice at 3-week intervals, then challenged 2 weeks after; and 100%, 100% and 50% mean of survival was observed in immunized mice with coated DNA vaccine by i.p., i.v. and s.c., respectively. Coated DNA vaccine showed significant immunogenicity and elicited protective levels of antigen specific IgG and its subclass antibody, an increased proportion of CD4(+) and CD8(+) T cells and INF-γ and IL-12 levels in the serum and cultured splenocyte supernatant, as well as INF-γ producing cells in the spleen. We demonstrate that, NP-coated MSP-1 DNA-based vaccine confers protection against lethal P. yoelii challenge in murine model across the various route of administration and may therefore, be considered a promising delivery system for vaccination.
    Vaccine 09/2011; 29(48):9038-50. DOI:10.1016/j.vaccine.2011.09.031 · 3.62 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Calcium oxide could be dispersed on zeolite NaY or NaZSM-5 to form strong basic sites on the host by the use of microwave radiation. After activation at 873 K, some CaO/NaY and CaO/NaZSM-5 composites possess an extraordinary high basic strength with H of 27. Moreover, these strong basic materials had a high water-stability.
    Studies in surface science and catalysis 01/2002; 142:175-182. DOI:10.1016/S0167-2991(02)80026-X
  • [Show abstract] [Hide abstract]
    ABSTRACT: Chronic diseases, particularly malignancies and immune-mediated inflammatory diseases (IMIDs), are a challenging frontier for clinical diagnosis and treatment, as well as for biomedical research. Current treatment regimens are frequently insufficient and thus new treatment strategies are needed. Novel therapies for disabling such diseases should provide improvements with respect to safety, efficacy and cost. To fulfill these three key criteria, recent research efforts have focused on the development of ‘smart drugs’. This review highlights some examples of the rapidly expanding possibilities that current biotechnology has to offer in the development of novel therapeutic strategies for complex diseases such as IMIDs. Special attention is given to advances in, and limitations of, controlled and targeted gene product application in inflammatory diseases.
    Trends in Biotechnology 06/2004; 22(6):304-310. DOI:10.1016/S0167-7799(04)00106-4 · 11.96 Impact Factor
Show more