Silica nanoparticles as a nonviral vector for in vivo gene therapy neither surface functionalized SiNp1 is neither “a cationic ion” nor a surface (encapsulation) nor SiNp2 (adsorption). p53 gene expression in the breast upon (i.v) administration. SiNp1 showed a 50- and 100-fold transfection activity, tumor growth inhibition, animal survival (80%), and high levels of p53 and Bax were detected in the sera of treated animals compared to SiNp2 or naked pCMV/p53, respectively. These results demonstrate for improvements in the both systems. This study suggests that nonviral vector systems will have important roles in achieving the impermanent gene transfer in vivo.