Novel Virus-Templated Engineered Material for Photodynamic Treatments

Thiophene-based materials <b>TMs</b>, due to their excellent electron transport properties, optical properties, soft material nature, stability, solution processability, and water dispersibility, have demonstrated significant potential in photodynamic (<b>PDT</b>) therapies. To increase the cell uptake and the permeation of physiological barriers recent studies reported the use of proteins (human serum albumin, HSA) [1] or phages (M13 bacteriophage) [2,3] as natural carriers of different photosensitizers (rose bengal, chlorin e6, oligothiophene ECB04), able to induce cell death by apoptosis in a variety of cell lines. Here we propose a novel engineered living material for photodynamic therapy, i.e. a virus-templated platform, based on the M13 bacteriophage<b>,</b> engineered to display targeting ligands on its surface. By covering the surface of the M13 phage with oligothiophene molecule, a 1-D thiophene nanoplatform, M13EGFR(TNP) was synthetized and tested in vitro and in vivo. Cell culture experiments were carried out to validate the ability of the biohybrid material to maintain the EGFR-targeted tropism of the phage and to demonstrate photoactivity. The tissue-like animal model Hydra was employed to further confirm the possibility to use these engineered materials for photodynamic treatment and to screen for targeting properties. The transparency, softness and body simplicity together with the lack of ethical issue make <i>Hydra</i> a suitable model for this type of studies, enabling fast screening of cytotoxicity and identification of molecular pathways underlying necrosis or apoptosis pathways. Our work provides valuable insights into the potential of M13EGFR(TNP) for targeted photodynamic therapy, laying the groundwork for further exploration of this innovative living material in <b>nanotheranostic</b> applications.<br/>[1] “Human Serum Albumin−Oligothiophene Bioconjugate: A Phototheranostic Platform for Localized Killing of Cancer Cells by Precise Light Activation”, <i>JACS Au</i> 2021, 1, 7, 925-935<br/>[2] “Orthogonal nanoarchitectonics of M13 phage for receptor targeted anticancer photodynamic therapy” <i>Nanoscale</i>. 2022; 14(3):632-641.<br/>[3] “Advanced photodynamic therapy with an engineered M13 phage targeting EGFR: Mitochondrial localization and autophagy induction in ovarian cancer cell lines” Free Radic Biol Med. 2022;179:242-251