Abstract
Ovarian cancer, which is one of the most diagnosed cancer types among women, maintains its significance as a global health problem. Several drug candidates have been investigated for the potential treatment of ovarian cancer. Nonsteroidal anti-inflammatory drugs (NSAIDs) demonstrated anti-cancer activity through the inhibition of cyclooxygenase 2 (COX-2) and by inhibiting COX-2-dependent prostaglandin (PG) production. Naproxen is one of the most used NSAIDs and Naproxen-derived compounds (NDCs) may show potential treatment effects on cancer as chemotherapeutic drugs. Although there are successful drug development studies, the lack of solubility of these drug candidates in aqueous media results in limited bioavailability and high variability of patient responses during treatment. Low aqueous solubility is one of the main problems in the pharmaceutical industry in terms of drug development. Nanotechnology-based strategies provide solutions to hydrophobic drug limitations by increasing dispersion and improving internalization. In this study, two different NDCs (NDC-1 and NDC-2) bearing a thiosemicarbazide/1,2,4-triazole moiety were synthesized and tested for chemotherapeutic effects on ovarian cancer cells, which have a high COX-2 expression. To overcome the limited dispersion of these hydrophobic drugs, the drug molecules were conjugated to the surface of 13 nm AuNPs. Conjugation of drugs to AuNPs increased the distribution of drugs in aqueous media, and NDC@AuNP conjugates exhibited excellent colloidal stability for up to 8 weeks. The proposed system demonstrated an increased chemotherapeutic effect than the free drug counterparts with at least 5 times lower IC50 values. NDC@AuNP nanosystems induced higher apoptosis rates, which established a simple and novel way to investigate activity of prospective drugs in drug discovery research.