| 학회 | 한국고분자학회 |
| 학술대회 | 2005년 가을 (10/13 ~ 10/14, 제주 ICC) |
| 권호 | 30권 2호 |
| 발표분야 | 고분자를 이용한 유전자 전달 |
| 제목 | Poly(amidoamine) dendrimer-grafted-dexamethasone as a nucleus targeting polymeric gene carrier |
| 초록 | Polyamidoamine (PAMAM) dendrimers contain large number of surface amines that are generation-dependent and are capable of forming polyplexes through the electrostatic interaction with polyanions, such as nucleic acids. So, PAMAM dendrimers have been very attractive to many scientists developing gene carriers because of their well-defined structure, ease of control of surface functionality, and relatively high gene transfection efficiency. We tried to prepare glucocorticoid-conjugated PAMAM dendrimer to make use of the glucocorticoid receptor-ligand interaction as it was successfully verified in cationic liposomal dexamethasone-mediated gene delivery research (Gruneich et al., 2004). Glucocorticoid receptor is a nuclear receptor, which binds to the glucocorticoid ligand in the presence of ligands enabling the translocation of receptor-ligand complex into the nucleus (Adcock & Caramori, 2001). It is also reported that the glucocorticoid receptor dilates the nuclear pore up to 60 nm during the translocation process, which is favorable for translocation of polymer/DNA complex into nucleus (Shahin et al., 2005). Therefore, it is presumed that, the transport of polymer/DNA complex into nucleus may be facilitated by the ligand-receptor mediated transport by conjugating the glucocorticoid ligand to the polymer that could form polyplexes with DNA, which may contribute to increase the exogenous gene expression efficiency of the polymer. To verify this hypothesis, the effect of glucocorticoid conjugation on the PAMAM polymer on the transfection efficiency was investigated. In this study, we report a steroid-conjugated polymer version, PAMAM-dexamethasone (PAM-Dexa), to introduce a nuclear targeting ligand to increase the transfection efficiency from the nucleus targeting functionality. We synthesized PAM-dexa and characterized its physicochemical properties, cytotoxicity, and in vitro transfection efficiency. As control polymeric gene carriers, polyethylenimine (PEI) and polyamidoamine (PAMAM) dendrimer were also used in the transfection experiments. The cytotoxicity and transfection efficiencies for 293 and Neuro 2A cells were measured by comparison with PEI and PAMAM. It was observed that dexamethasone conjugation enhanced the transfection efficiency of PAMAM. Therefore, the technique with dexamethasone may be useful for the gene delivery using polymeric gene carriers and the development of efficient polymeric vectors. 1. Adcock IM, Caramori G (2001) Cross-talk between pro-inflammatory transcription factors and glucocorticoids. Immunol. Cell. Biol. 79:376-384. 2. Gruneich JA, Price A, Zhu J, Diamond SL (2004) Cationic corticosteroid for nonviral gene delivery. Gene Ther. 11:668-674. 3. Shahin V, Albermann L, Schillers H, Kastrup L, Schafer C, Ludwig Y, Stock C, Oberleithner H (2005) Steroids dilate nuclear pores imaged with atomic force microscopy. J. Cell. Physiol. 202:591-601. |
| 저자 | 최준식1, 이민형2 |
| 소속 | 1충남대, 2한양대 |
| 키워드 | PAMAM dendrimer; dexamethasone |
