The main objective in gene therapy of brain tumors is to develop efficient, low toxic, and brain-targeting gene delivery systems which can cross the blood-brain barrier (BBB) and deliver therapeutic gene to the brain cancerous tissues. In this study, we designed and constructed a novel gene delivery systems (Tat-MS-PAMAM) by modifying the magnetosome (MS) with polyamidoamine (PAMAM) dendrimers and Tat peptides for the first time. Tat-MS-PAMAM readily formed polyplexes with the luciferase reporter plasmid (pGL-3) and improved plasmid complexation and stability against polyanion and DNase I. Transfection efficiencies of Tat-MS-PAMAM polyplexes with pGL-3 were studied using U251 human glioma cells in vitro. The result showed that the incorporation of external magnetic field and Tat peptides could significantly improve transfection efficiency of delivery system. Furthermore, biodistribution in vivo demonstrated that Tat-MS-PAMAM could efficiently transport across the BBB and assemble at brain tissue of rat detected by single photo emission computed tomography. Thus, with the multifunction of magnetic targeting, BBB transporting, and efficient gene transfecting, Tat-MS-PAMAM might be a novel nonviral delivery system for gene therapy of brain tumors. (C) 2011 Wiley Periodicals, Inc. J Appl Polym Sci 121: 3446-3454, 2011