The HIV-1 TAT peptide was dimerized and used to formulate a nanoparticle vector (dTAT NP) to leverage efficient tumor-targeted gene delivery following intratracheal administration. In vitro expression efficiency for dTAT NP–encapsulated luciferase or angiotensin II type 2 receptor (AT2R) plasmid DNA (pDNA) revealed effective pDNA transfection with negligible cytotoxicity. In orthotopic tumor grafts, immunohistochemical analysis confirmed that dTAT NP successfully delivered pDNA to the tumor, and gene expression in tumor tissues persisted at least 14 days after intratracheal administration. Bolus administration of dTAT NP–encapsulated AT2R or TRAIL pDNA, both endogenous apoptosis inducers, markedly attenuated tumor growth. For details, see article by Kawabata and colleagues on page 2057 of this issue.