Publication date: 22nd April 2022
In the last years, photodynamic therapy (PDT) has been widely used for clinical treatment of several types of cancer (head and neck, brain, lungs, pancreas, skin, etc.), since its minimal invasiveness. In PDT, a compound with photosensitizing properties (the photosensitizer, PS) is accumulated in cells and activated by light; in the presence of oxygen, the activated PS generates reactive oxygen species (ROS) that are cytotoxic for the neoplastic cells. The use of biological carriers for the PS compounds augments the internalization and the specific targeting inside cells and tissues. Recent studies reported the use of proteins (human serum albumin, HSA) [2] or phages (M13 bacteriophages ) [2,3] as carriers of different photosensitizers (rose bengal, chlorin e6, oligothiophene ECB04), showing the possibility to induce cell death by apoptosis in cancer cell lines. As known, the use of in vitro models has intrinsic limitations due to the lack of a behavioral and a full-body response, while on the other hand the use of mammalian models implies a long series of ethical limitations. Here we propose a new invertebrate model, the freshwater polyp Hydra vulgaris, to study at simple level the effect of the latest generation of photodynamic therapy. The transparency, softness and body simplicity together with the lack of ethical issue and limitation make Hydra a suitable model for this type of studies, allowing us to observe immediately the effect of induced cell death (necrosis and apoptosis). By challenging the polyps with HSA and phagesfunctionalized with ECB04, preliminary data shown at animal level the induction of cell death with a similar output for all the tested systems and the modulation of gene expression of the ROS and apoptosis related pathways.
[1] “Human Serum Albumin−Oligothiophene Bioconjugate: A Phototheranostic Platform for Localized Killing of Cancer Cells by Precise Light Activation”, Andrea Cantelli et al., JACS Au 2021, 1, 925-935
[2] “Orthogonal nanoarchitectonics of M13 phage for receptor targeted anticancer photodynamic therapy”, Luca Ulfo et al., Nanoscale. 2022 Jan 20;14(3):632-641. doi: 10.1039/d1nr06053h. PMID: 34792088.
[3] “Advanced photodynamic therapy with an engineered M13 phage targeting EGFR: Mitochondrial localization and autophagy induction in ovarian cancer cell lines”, Barbara Bortot et al., Free Radic Biol Med. 2022 Feb 1;179:242-251. doi: 10.1016/j.freeradbiomed.2021.11.019. Epub 2021 Nov 19. PMID: 34808331.