Issue 3, 2022

Orthogonal nanoarchitectonics of M13 phage for receptor targeted anticancer photodynamic therapy

Abstract

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.

Graphical abstract: Orthogonal nanoarchitectonics of M13 phage for receptor targeted anticancer photodynamic therapy

Article information

Article type
Paper
Submitted
14 Sep 2021
Accepted
11 Nov 2021
First published
12 Nov 2021

Nanoscale, 2022,14, 632-641

Orthogonal nanoarchitectonics of M13 phage for receptor targeted anticancer photodynamic therapy

L. Ulfo, A. Cantelli, A. Petrosino, P. E. Costantini, M. Nigro, F. Starinieri, E. Turrini, S. K. Zadran, G. Zuccheri, R. Saporetti, M. Di Giosia, A. Danielli and M. Calvaresi, Nanoscale, 2022, 14, 632 DOI: 10.1039/D1NR06053H

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