This technology is a novel method of delivering therapeutics and imaging molecules to the brain using the filamentous bacteriophage M13. M13 phage are an attractive candidate for a molecular courier due to their small diameter (~5-6nm), rod-like shape, and the ability to modify coat proteins to attach functional molecules. These inventors made two major improvements to M13 phage to increase BBB penetration and GBM targeting. Firstly, they decreased the length of the phage. M13 phage length is directly proportional to the size of the packaged genome, so these inventors devised a two plasmid system to decrease the size of the packaged ssDNA genome. One plasmid contains all of the coding information for the protein coat and packaging components, and the second contains only ssDNA of tunable length containing a packaging signal. By changing the size of the plasmid with the packaging signal, the length of the M13 phage can be finely tuned between 880nm for a wild type phage down to only 50nm for phage with a packaged genome of 285 DNA base pairs. Secondly, the inventors included a chlorotoxin (CTX) motif on the M13 phage. CTX has a high positive charge that aids in BBB penetration and has additionally been shown to target very specifically to the electronegative GBM extracellular matrix. The combined M13-CTX delivery system results in highly efficient BBB penetration and GBM targeting while additionally facilitating addition of therapeutic or imaging molecules to the M13 coat proteins. As a proof of principle, the inventors attached single walled carbon nanotubes (SWNT) to the M13-CTX phage and injected the composition into an in vivo mouse model of GBM. The SWNT-M13-CTX phage demonstrated efficient tumor targeting and facilitated sub-millimeter resolution near infrared imaging of the
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