Folic acid–encapsulated silver nitroprusside nanoparticles for targeted therapy in ovarian cancer

Ovarian cancer is the most prevalent fatal, gynecological malignancy in women, resulting in poor survival rate (fifth in cancer deaths) due to its asymptomatic nature. Unmet medical challenges for ovarian cancer are associated with several constraints such as poor bioavailability, nonspecificity, and toxicity-related issues. Targeted drug delivery systems may overcome the existing limitations. Utilizing the concept of overexpression of folate receptors (FRs) in ovarian carcinoma, we have designed FRs-targeted drug delivery systems (AgNNPs-FA) by combining silver nitroprusside nanoparticles (AgNNPs) because of their inherent anticancer properties, as established by our group, and folic acid (FA) as targeting agent that attack FRs in this study. Initially, both AgNNPs and AgNNPs-FA were designed and later characterized using several analytical tools such as dynamic light scattering, x-ray diffraction, scanning electron microscopy, transmission electron microscopy, thermogravimetric analysis, high-performance liquid chromatography, and Fourier transform-infrared spectroscopy, etc. The<i>in vitro</i>cell viability assay in a Chinese hamster ovary cell line suggests the biocompatible nature of AgNNPs-FA. The targeted anticancer activity of the AgNNPs-FA is established in human ovarian adenocarcinoma (SK-OV-3) via several<i>in vitro</i>assays and compared with AgNNPs. All<i>in vitro</i>assays (cell viability assay, thymidine incorporation assay, scratch assay, cell cycle, apoptosis assay, and tunnel assay) in SK-OV-3 and<i>in vivo</i>experiments (chorioallantoic membrane assay) in fertilized eggs with AgNNPs-FA exhibit more anticancer activity in a targeted fashion than AgNNPs. The plausible mechanisms behind the anticancer activity of the nanoparticles were demonstrated using the ROS assay (DCFDA and DHE staining), JC-1 staining, immunocytochemistry staining (Ki-67), and Western blot analysis. The results altogether support the idea that this targeted drug delivery system could be used as an alternative treatment strategy for ovarian cancer and other cancers with the overexpression of FRs.