These results demonstrate the ability to design and produce polymer-based nanodevices for the intracellular targeting of drugs, imaging agents, and other materials.

Gene transfer to the lung can be achieved via either the airway or the pulmonary vasculature. We evaluated gene transfer and expression by intravascular and endobronchial routes, using DNA complexed with G9 PAMAM dendrimer or naked plasmid DNA. Intravascular tail vein delivery of dendrimer-complexed pCF1CAT plasmid resulted in high levels of transgene expression in the lung at 12 and 24 hr, followed by a second peak of expression 3 to 5 days after administration. After intravenous administration of the complexes, CAT expression was never observed in organs other than the lung. There were only minimal levels of CAT protein expressed in the lung after intravenous administration of naked plasmid DNA. Repeated intravascular doses of the dendrimer-complexed plasmid, administered four times at 4-day intervals, maintained expression at 15-25% of peak concentrations achieved after the initial dose. Endobronchial delivery of naked pCF1CAT plasmid produced significant amounts of CAT protein in the lung. Comparison of intratracheal and intranasal routes resulted in similar expression levels of CAT in the lung and trachea. However, in juxtaposition to vascular delivery, intranasal delivery of dendrimer-complexed plasmid DNA gave lower levels of CAT expression than that observed with naked plasmid DNA. In situ localization of CAT enzymatic activity suggested that vascular administration seemed to achieve expression in the lung parenchyma, mainly within the alveoli, while endobronchial administration primarily targeted bronchial epithelium. Our results show that intravenously administered G9 dendrimer is an effective vector for pulmonary gene transfer and that transgene expression can be prolonged by repeated administration of dendrimer-complexed DNA.

Gene transfer in the lung holds promise for the treatment for 5 days thereafter. When DNA was delivered in a 50% of diseases such as pulmonary fibrosis, cystic fibrosis and suspension of Exosurf, the expression of either CAT or asthma. Pulmonary surfactant has been reported to Luc was significantly reduced by 89.6 ± 1.4% and enhance expression from endobronchial, adenovirus-82.7 ± 10.5%, respectively. The decrease in Luc mediated gene transfer in experimental animals. This study expression was closely correlated (r = 0.99, P Ͻ 0.001) to examines the effect of exogenous synthetic surfactant log concentration of surfactant in the plasmid buffer sol-(Exosurf) on gene expression from naked plasmid DNA ution (IC 50 = 8.6%). CAT expression was not altered when administered endobronchially to adult mice. Transfection surfactant was administered either 2 h before or after plasefficiency was evaluated by quantifying the expression of mid DNA instillation. Examination of the components of chloramphenicol acetyltransferase (CAT) and luciferase Exosurf revealed that two compounds, DPPC and tylox-(Luc) genes in the lung. Endobronchial administration of apol, showed inhibitory effects on CAT expression. Howeither CAT or Luc expression plasmid DNA resulted in ever, the inhibition caused by Exosurf appeared greater detectable concentrations of each reporter protein. CAT than that of either component. Our results suggest that the expression from plasmid DNA was monitored after endolung surfactant is a barrier to transfection of the endobronchial administration with the maximal expression bronchial airway and may be partly responsible for the low observed at 3-5 days after administration and decreasing expression of exogenous DNA in vivo in the bronchial tree.

Nanotechnology provides the sized materials that can be synthesized and function in the same general size range and Biologic structures. We have attempted to develop forms of anticancer therapeutics based on nanomaterials. Our project seeks to develop dendritic polymer nanodevices that serve as a means for the detection of cancer cells, the identi®cation of cancer signatures, and the targeted delivery of anti-cancer therapeutics (cis-platin, methotrexate, and taxol) and contrast agents to tumor cells. Initial studies documented the synthesis and function of a targeting module, several drug delivery components, and two imaging/contrast agents. Analytical techniques have been developed and used to con®rm the structure of the device. Progress has been made on the speci®cally triggered release of the therapeutic agent within a tumor using high-energy lasers. The work to date has demonstrated the feasibility of the nano-device concept in actual cancer cells in vitro.

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