| |
| Purpose: Chlorotoxin (CTX) was exploited as the targeting ligand to conjugate the nanoscopic high-branching dendrimer, polyamidoamine (PAMAM), via bifunctional polyethyleneglycol (PEG), yielding PAMAM-PEG-CTX. After complexing with DNA, a novel glioma-targeting gene delivery system was constructed. Methods and Results: The cellular uptake of CTX itself was observed apparently in C6 glioma cells, almost not in 293 cells. The modification of CTX could significantly increase the cellular uptake of vectors and the DNA-loaded nanoparticles (NPs) in C6 cells. The in vivo distribution of PAMAM-PEG-CTX/DNA NPs in the brain was higher than that of PAMAM/DNA NPs and PAMAM-PEG/DNA NPs. Furthermore, the gene expression of PAMAM-PEG-CTX/DNA NPs was higher and boarder in glioma than that of unmodified and PEG-modified counterparts. The TUNEL analysis showed a more wide-extended apoptosis in the CTX-modified group, compared to other groups including commercial temozolomide group. The median survival time of CTX-modified group was 59.5 days, significantly longer than that of other groups. Conclusion: The results suggested that CTX could be exploited as a special glioma-targeting ligand, and PAMAM-PEG-CTX/DNA NPs is a potential non-viral delivery system for gene therapy of glioma via intravenous administration. |
|
| Keywords:pharmaceutics; chlorotoxin; polyamidoamine; glioma-targeting; gene therapy |
|
