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Orthogonal nanoarchitectonics of M13 phage for receptor targeted anticancer photodynamic therapy

2021; Royal Society of Chemistry; Volume: 14; Issue: 3 Linguagem: Inglês

10.1039/d1nr06053h

2040-3372

Luca Ulfo, Andrea Cantelli, A. Petrosino, Paolo Emidio Costantini, Michela Nigro, Francesco Starinieri, Eleonora Turrini, Suleman Khan Zadran, Giampaolo Zuccheri, Roberto Saporetti, Matteo Di Giosia, Alberto Danielli, Matteo Calvaresi,

Bacteriophages and microbial interactions

Photodynamic therapy (PDT) represents a promising therapeutic modality for cancer. Here we used an orthogonal nanoarchitectonics approach (genetic/chemical) to engineer M13 bacteriophages as targeted vectors for efficient photodynamic killing of cancer cells. M13 was genetically refactored to display on the phage tip a peptide (SYPIPDT) able to bind the epidermal growth factor receptor (EGFR). The refactored M13EGFR phages demonstrated EGFR-targeted tropism and were internalized by A431 cancer cells, that overexpress EGFR. Using an orthogonal approach to the genetic display, M13EGFR phages were then chemically modified, conjugating hundreds of Rose Bengal (RB) photosensitizing molecules on the capsid surface, without affecting the selective recognition of the SYPIPDT peptides. Upon internalization, the M13EGFR-RB derivatives generated intracellularly reactive oxygen species, activated by an ultralow intensity white light irradiation. The killing activity of cancer cells is observed at picomolar concentrations of the M13EGFR phage.