Fd-tet filamentous phage is a biological nanowire (~900 nm long and 7 nm wide) non-toxic to human beings and made up of ordered protein shell encasing ssDNA core. Its major protein shell (side wall) is composed of ~3900 copies of a major coat protein (called pVIII) to which cancer targeting peptides can be genetically fused. Here, we describe a novel nanocomposite wire, which is formed by chemically conjugating the phage bionanowire and photosensitizer, and employ the resultant complex bionanowire for selective cancer cell killing through the generation of cytotoxic singlet oxygen via a mechanism of photodynamic therapy (PDT). PDT is an established noninvasive medical treatment procedure which integrates oxygen, photosensitizer and light to generate singlet oxygen for tumor destruction. We first conjugated a porphyrin, pyropheophorbid-a (PPa), to the surface of SKBR-3 breast cancer cell-specific fd-tet phage to form a novel bionanowire called PPa-phage complex. We studied the morphological and spectroscopic changes of the complex as well as the production of singlet oxygen, and demonstrated its use in in vitro targeted cancer cell destruction.We believe that the formation of photosensitizer-phage nanowires is a versatile approach to nanotherapeutics since any filamentous bacteriophage, specific to a given organ or tissue, can be first selected by using the phage display technique, and then conjugated with a photosensitizer of interest to form a novel target-specific phage-photosensitizer nanowire. This work opens up new avenues for the development of next generation target specific photosensitizers that can be used for clinical applications in PDT.

Photosensitizer-modified phage bionanowires for selective cancer cell killing

247th National Meeting (2014)

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