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Self-assembly of 13 nm gold nanoparticles (AuNPs) engineered into 2D structures in solution using DNA tiles for their possible use for gene delivery and photothermal therapy is reported. The two different DNA tiles were constructed and the AuNPs coated with oligonucleotides possessing complementary sequence from the free ends were hybridized with the sticky ends of the tiles. The DNA tiles were bind to each other by mixing the tile structures without a heating and cooling step. The constructed nanostructures were 5 to 7 DNA tiles long since heat was not used to elongate them. When the DNA tiles were bound to the AuNPs, it was observed that AuNPs tend to stay in close proximity by filling the gaps between tiles. The stability of the constructed structures was tested against DNase, a DNA cleaving enzyme, for possible applications for gene delivery and photothermal therapy. It was found that the AuNP bound DNA tile structures resist the DNase cleavage up to eighty percent. Due to the presence of the AuNPs in the structure, the enzyme cannot bind to DNA sequences and this increases the DNA tile structures' stability. © 2012 AY, Sonay, et al.