Ovarian cancer is the fifth most frequent cause of death in women, claiming the highest mortality rate within gynecological cancers.[1] The standard of care for advanced-stage ovarian cancer is surgical debulking and platinum-based chemotherapy, followed by maintenance treatment with PARP inhibitors and/or bevacizumab. Despite these, the majority of women face relapse, resulting in a concerning 5-year survival rate of approximately 30%.[2] To mitigate treatment-associated toxicity while augmenting therapeutic outcomes, targeted therapies emerge as promising avenues. Folate receptor (FR) is overexpressed in over 70% of primary and 80% of recurrent ovarian cancers. Additionally, the expression of FR has been shown to remain high after chemotherapy.[3] Photodynamic therapy (PDT) is a minimally invasive treatment in which administration of a light-activated drug is followed by irradiation at a specific wavelength leading to the production of cytotoxic reactive oxygen species.[4] Verteporfin (VP) is a well-known photosensitizer that presents low aqueous solubility and has been approved by the Food and Drug Administration (FDA) as a liposomal formulation.[4]
Leveraging VP's potential and FR specificity, a novel approach (VP-NPs) emerges for the targeted PDT of ovarian cancer. A novel VP-derived molecule was first developed to enhance encapsulation efficiency into nanoparticles. Cellular uptake studies were conducted in FR-positive ovarian cancer cells, and phototoxicity was assessed upon irradiation. Biocompatibility assays were performed to evaluate the safety profile of VP-NPs in vitro. VP-NPs exhibited increased photoactivity, singlet oxygen production and biocompatibility relative to the VP-derived molecule alone. Furthermore, VP-NPs demonstrated superior PDT efficiency and showed increased cellular uptake by FR-positive ovarian cancer cells compared to non-targeted nanoparticles. Our study highlights the potential of VP-NPs as a targeted PDT agent for ovarian cancer therapy, offering improved biocompatibility, specificity, and therapeutic efficiency. These findings lay the groundwork for further investigation and potential clinical application of VP-NPs in ovarian cancer treatment.