Rose Bengal (RB) is a photosensitizer (PS) used in anti-cancer and anti-bacterial photodynamic therapy (PDT). The specific excitation of this PS allows the production of singlet oxygen and oxygen reactive species that kill bacteria and tumor cells. In this review, we summarize the history of the use of RB as a PS coupled by chemical or physical means to nanoparticles (NPs). The studies are divided into PDT and PDT excited by X-rays (X-PDT), and subdivided on the basis of NP type. On the basis of the papers examined, it can be noted that RB used as a PS shows remarkable cytotoxicity under the effect of light, and RB loaded onto NPs is an excellent candidate for nanomedical applications in PDT and X-PDT.

Despite conventional treatment combining complete macroscopic cytoreductive surgery (CRS) and systemic chemotherapy, residual microscopic peritoneal metastases (mPM) may persist as the cause of peritoneal recurrence in 60% of patients. Therefore, there is a real need to specifically target these mPM to definitively eradicate any traces of the disease and improve patient survival. Therapeutic targeting method, such as photodynamic therapy, would be a promising method for such a purpose. Folate receptor alpha (FRα), as it is specifically overexpressed by cancer cells from various origins, including ovarian cancer cells, is a good target to address photosensitizing molecules. The aim of this study was to determine FRα expression by residual mPM after complete macroscopic CRS in patients with advanced high-grade serous ovarian cancer (HGSOC). A prospective study conducted between 1 June 2018 and 10 July 2019 in a single referent center accredited by the European Society of Gynecological Oncology for advanced EOC surgical management. Consecutive patients presenting with advanced HGSOC and eligible for complete macroscopic CRS were included. Up to 13 peritoneal biopsies were taken from macroscopically healthy peritoneum at the end of CRS and examined for the presence of mPM. In case of detection of mPM, a systematic search for RFα expression by immunohistochemistry was performed. Twenty-six patients were included and 26.9% presented mPM. In the subgroup of patients with mPM, FRα expression was positive on diagnostic biopsy before neoadjuvant chemotherapy for 67% of patients, on macroscopic peritoneal metastases for 86% of patients, and on mPM for 75% of patients. In the subgroup of patients with no mPM, FRα expression was found on diagnostic biopsy before neoadjuvant chemotherapy in 29% of patients and on macroscopic peritoneal metastases in 78% of patients. FRα is well expressed by patients with or without mPM after complete macroscopic CRS in patients with advanced HGSOC. In addition to conventional cytoreductive surgery, the use of a therapeutic targeting method, such as photodynamic therapy, by addressing photosensitizing molecules that specifically target FRα may be studied.

A semi‐heterogeneous photocatalytic system was assembled through encapsulation of a lipophilic porphyrin in stabilized polydiacetylene micelles. The colloidal nanohybrid catalyst was valorized in the aerobic photo‐oxidation of sulfides to the corresponding sulfoxides. Micelles behaved as nanoreactors by creating a favorable environment for the photo‐activation of oxygen nearby thioethers and subsequent sulfoxidation. The process operates selectively under visible light and air atmosphere, with low catalytic loading and in water as the only solvent.

Immunogenic cell death (ICD), which converts tumor cells into their own vaccine, plays a pivotal role in the development of novel anti-cancer therapies. Here, a small series of osmium(II) polypyridyl complexes were synthesized and their biological activity in the dark and upon light irradiation against various cancer cell lines was studied. The compound Os2 (bearing two 4,7-diphenyl-1,10-phenanthrolines and one substituted bipyridine ligand) was discovered to be the most effective photosensitizer (PS) for photodynamic therapy (PDT) of this series through the photogeneration of 1O2 and •OH. In addition, Os2 was found to exhibit promising toxicity upon near-infrared (NIR) irradiation under both normoxia and hypoxia. These observations indicate that this PS is working through a mixture of Type-I and Type-II mechanisms. More interestingly, upon 740 nm irradiation, Os2 can stimulate a strong ICD response both in vitro and in vivo. A comprehensive immune analysis showed that mice vaccinated with Os2-treated CT26-luc cells boosted the systemic specific adaptive immune responses, including the activation of CD8+ T cells and reprograming of macrophages, leading to effective inhibition of tumor growth. Os2 is, to the best of our knowledge, the first photoactive osmium-based complex inducing ICD.

Epithelial ovarian cancer (EOC) remains a leading cause of gynecologic cancer-related mortality, with frequent relapse and the emergence of resistance to platinum-based chemotherapy and PARP inhibitors (PARPi). Innovative therapeutic strategies are therefore needed, particularly for patients displaying intrinsic or acquired resistance to PARPi. Photodynamic therapy (PDT) could be a good therapeutic alternative. PDT represents a locoregional treatment modality that induces tumor cell death through light-activated reactive oxygen species generation. In this study, we evaluated the activity of a folate receptor alpha (FRα)-targeted photosensitizer (Pyro-PEG-FA) in ovarian cancer models, including patient-derived tumor organoids (PDTOs) exhibiting resistance to olaparib. FRα expression and photosensitizer uptake were confirmed in ovarian cancer cell lines, 3D spheroids, and two independent PARPi-resistant PDTO models. Targeted PDT induced a dose-dependent decrease in viability across all models tested. Importantly, PDT maintained cytotoxic activity in PDTOs resistant to PARPi. In contrast, sequential combination of PARPi and PDT did not demonstrate additive or synergistic effects, as PDT alone was sufficient to induce substantial tumor cell death. These findings indicate that FRα-targeted PDT retains efficacy in PARPi-resistant ovarian cancer organoid models and support its further investigation as a potential therapeutic option in the context of treatment-resistant EOC.

Le cancer épithélial de l'ovaire demeure le cancer gynécologique le plus meurtrier, avec un taux de rechute supérieur à 60 % chez les patientes traitées par chirurgie cytoréductrice maximale et chimiothérapie à base de platine. L'un des principaux obstacles est la persistance de métastases péritonéales microscopiques, non détectables après la chirurgie, qui réduisent considérablement les chances de survie des patientes. La thérapie photodynamique (PDT) apparaît comme une stratégie prometteuse pour éliminer ces lésions résiduelles. Cependant, la spécificité limitée des photosensibilisateurs (PS), qui s'accumulent aussi dans les tissus sains, engendre des effets secondaires indésirables. L'utilisation de l'acide folique (AF), se liant spécifiquement aux récepteurs aux folates alpha (FR⍺) surexprimés dans les cellules cancéreuses ovariennes, offre une solution. Cette thèse propose de nouveaux analogues de l'AF (AAF) pour améliorer la stabilité et l'affinité des PS pour FR⍺, augmentant ainsi la spécificité et l'efficacité de la PDT. Quatre axes principaux sont abordés : (1) le développement d'un analogue de l'AF (AAF1) conjugué à la pyrophéophorbide a pour cibler les métastases ovariennes ; (2) une étude comparative de la stabilité de l'AF et de ses analogues ; (3) l'influence de la position de couplage sur les propriétés biologiques du PSAAF1 ; et (4) la synthèse de PS de troisième génération ciblant le récepteur NRP-1 pour le traitement du cancer du poumon. Ces travaux apportent des avancées significatives pour une PDT plus ciblée et efficace dans le traitement des cancers de l'ovaire et du poumon.