| 초록 |
Gene therapy presents a promising approach for the treatment of human disease. The aim of the gene therapy is to introduce a gene into cells either indirectly or directly for treatment of human diseases. Recently, there has been much interest in developing new formulations and materials for delivering foreign DNAs. Viral delivery systems have been used in many applications and clinical trials; however, the immune response to viral proteins continues to be a daunting problem. Lipid-based systems represent a promising class of gene carriers; however, their toxicity on repeated dosing and poor in vivo performance are major drawbacks in advancing them to the clinic. Therefore, there has been considerable interest in developing polymeric material as gene delivery vehicles. PPD as the novel highly branched molecule, has various molecular weights and a large number of controllable peripheral functionalities. Compared with another linear and branched polymers, the controllable surface functionality makes the dendrimers interesting class of gene delivery vehicles. A recent report showed that the PPD containing terminal amino groups has high transfection efficiency. In spite of many advantages of PDD, the PDD has not been developed to introduce foreign DNAs into specific cells. The receptor-mediated endocytosis systems of various cell types can be useful for tissue-specific delivery, and several gene delivery systems have been developed to introduce foreign DNAs into specific cells through this receptor-mediated endocytosis. G-PDD wil be expected to have specificity for targeting tumor cells. One of the most common and profound phenotypes of highly malignant tumors, as known for more than seven decades, is their ability to metabolize glucose at high rates, even though all mammalian cell membranes contain proteins involved in the glucose transport. We prepared glucosylated polypropyleneimine dendrimer (G-PPD) as a tumor-targeting gene carrier through facilitative glucose metabolism by tumor glucose transporter. The G-PDD/DNA complex formation was confirmed by electrophoresis on agarose gel. Particle sizes and zeta potential were measured using dynamic light scattering. Cytotoxicity test was checked by cell proliferation assay kit with several cells. The in vitro transfection in the several cells was checked by luciferase assay. Especially, glucosylation of the primary amino group of PPD at high substitution degree will be expected to confer tumor-targeting property through facilitative glucose metabolism by the glucose transporters in tumors, and decreased cellular toxicity. |
