Investigation of Gold Nanoparticle Naproxen-Derived Conjugations in Ovarian Cancer

Ovarian cancer, which is one of the most diagnosed cancertypesamong women, maintains its significance as a global health problem.Several drug candidates have been investigated for the potential treatmentof ovarian cancer. Nonsteroidal anti-inflammatory drugs (NSAIDs) demonstratedanti-cancer activity through the inhibition of cyclooxygenase 2 (COX-2)and by inhibiting COX-2-dependent prostaglandin (PG) production. Naproxenis one of the most used NSAIDs and Naproxen-derived compounds (NDCs)may show potential treatment effects on cancer as chemotherapeuticdrugs. Although there are successful drug development studies, thelack of solubility of these drug candidates in aqueous media resultsin limited bioavailability and high variability of patient responsesduring treatment. Low aqueous solubility is one of the main problemsin the pharmaceutical industry in terms of drug development. Nanotechnology-basedstrategies provide solutions to hydrophobic drug limitations by increasingdispersion and improving internalization. In this study, two differentNDCs (NDC-1 and NDC-2) bearing a thiosemicarbazide/1,2,4-triazolemoiety were synthesized and tested for chemotherapeutic effects onovarian cancer cells, which have a high COX-2 expression. To overcomethe limited dispersion of these hydrophobic drugs, the drug moleculeswere conjugated to the surface of 13 nm AuNPs. Conjugation of drugsto AuNPs increased the distribution of drugs in aqueous media, andNDC@AuNP conjugates exhibited excellent colloidal stability for upto 8 weeks. The proposed system demonstrated an increased chemotherapeuticeffect than the free drug counterparts with at least 5 times lowerIC50 values. NDC@AuNP nanosystems induced higher apoptosis rates,which established a simple and novel way to investigate activity ofprospective drugs in drug discovery research.