Apoptin Gene Delivery by the Functionalized Polyamidoamine Dendrimer Derivatives Induces Cell Death of U87-MG Glioblastoma Cells

作者：Bae Yoonhee; Rhim Hyang Shuk; Lee Seulgi; Ko Kyung Soo; Han Jin^*; Choi Joon Sig^*

来源：Journal of Pharmaceutical Sciences, 2017, 106(6): 1618-1633.

DOI：10.1016/j.xphs.2017.01.034

• apoptin
• nonviral gene delivery
• apoptosis
• U87-MG glioblastoma cells

Malignant glioma is the most common and aggressive form of primary brain tumor in adults. In this study, we describe the efficacy of nonviral gene delivery carriers, histidine-and arginine-or histidine- and lysine-grafted polyamidoamine (PAMAM) dendrimers (PAMAM-H-R and PAMAM-H-K), in delivering a therapeutic and a tumor-selective killer gene, apoptin, using human glioma cells (U87-MG) and newborn human dermal fibroblast cells. We analyzed transfection efficiency using luciferase and a plasmid DNA encoding for enhanced green fluorescent protein and assessed cell viability in both cells. The results show that transfection efficiency of PAMAM-H-R and PAMAM-H-K was greatly increased compared with that of native PAMAM. Moreover, among PAMAM derivatives, cytotoxicity of PAMAM-H-K was very low. We treated both cells with complexes of PAMAM-H-R or PAMAM-H-K and apoptin and analyzed their cellular uptake by flow cytometry and localization by confocal microscopy. Furthermore, cell cycle distribution, caspase 3 activity assay, and JC-1 analysis showed cell death induced by apoptin in U87-MG cells. The present study demonstrates that a PAMAM-H-R/apoptin complex is an effective gene carrier system in glioma cell culture.

• 出版日期2017-6