Cancerous tumors require a blood supply for the delivery of nutrients and removal of wastes. This is accomplished by stimulating new blood vessel formation as the tumor grows. These blood vessels can be an ideal target for therapy for a variety of reasons. The tumor vasculature is accessible to therapeutic agents. The blood vessel (endothelial) cells, unlike the cancer cells, are genetically stable. This means that therapeutics targeted to the endothelial cell markers will not become ineffective due to changing targets. New and developing blood vessels express a transmembrane protein, α_Vβ₃ integrin that established quiescent (not growing) blood vessels do not. A nine amino acid peptide has been identified that binds to this integrin and has been examined for targeting delivery of therapeutic molecules to tumor neovasculature. This peptide has the amino acid sequence Cysteine-Aspartic acid-Cysteine-Arginine–Glycine-Aspartic acid-Cysteine-Phenylalanine-Cysteine and is referred to as RGD-4C. This peptide can be used to target molecules that inhibit new blood vessel formation (antiangiogenic) or destroy the existing vasculature. Many types of nanoparticles have been examined as drug delivery vehicles, including radial polymers called dendrimers. Ethylenediamine-core polyamidoamine (PAMAM) dendrimers are dense radial polymers that contain a central ethylenediamine core, with each tertiary amine nitrogen carrying two branched amidoamine groups. For each generation, two additional branches are added to the terminal amino (-NH2) groups. Thus, each arm of the dendrimer is split into an additional two branches at each tertiary amine. The terminal primary amines remain reactive for further conjugation, while the internal tertiary amines are very stable. A generation 5 PAMAM dendrimer has a measured diameter of 5.4 nm with 128 terminal functional amine groups available for conjugating a variety of therapeutic, targeting and imaging molecules. Interleukin-12 (IL-12) is a regulatory cytokine involved in the initiation and regulation of the cellular immune response. IL-12 is produced by a variety of cells including macrophages, monocytes, dendritic cells, and B cells typically in response to a foreign immunostimulating molecule. IL-12 causes the production of interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) from both natural killer (NK) cells and helper T cells. IL-12, through its stimulation of IFN-γ production, enhances the immune response to cancers in mice and protects against metastases. However, it can be toxic when delivered systemically. In previous research, targeting delivery of IL-12 to a tumor site using a protein fusion with RGD-4C resulted in localization at the tumor site, expression of IFN-γ, decreases in cytotoxicity, and increased angiogenesis. Using PAMAM dendrimers as delivery vehicles for the targeting molecule (RGD-4C) and the therapeutic IL-12 will allow controlled ratios of moieties for optimal cellular internalization and stimulation of IFN-γ. We have conjugated the RGD-4C to a generation 5 PAMAM dendrimer and a fluorescent molecule for detection purposes. We will present binding of the loaded dendrimer to α_Vβ₃ integrin positive and negative cells, optimization of IL-12 and RGD-4C conjugation method, and the cytotoxic effects of the dendrimer and conjugated dendrimer in vitro.