Investigation of Gold Nanoparticle Naproxen-Derived Conjugations in Ovarian Cancer

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.

Strategic Assessment of Boron-Enriched Carbon Dots/Naproxen: Diagnostic, Toxicity, and In Vivo Therapeutic Evaluation

“…Consistent with the findings from flow cytometry analysis (Figure b), we found that when B-CDs were combined with naproxen, a considerable cancer-killing efficacy was demonstrated through cytotoxicity evaluation. It appears that naproxen played a role in the cellular disruption of DNA conformation. , …”

“…In the face of the ongoing investigation into toxicity, the integration of nanoparticles into drug delivery systems remains achievable through active or passive targeting mechanisms. − Drug loading processes encompass physical and chemical approaches, where physical encapsulation offers simplicity and cost-effectiveness but may suffer from off-targeted molecular degradation. , Conversely, chemical conjugation with polymer materials provides advantages such as hydrophobic drug solubility, controlled pharmacokinetics, and reduced drug release in large quantities. , A previous study evaluated tetrazine-functionalized boron-rich carbon dots, which demonstrated rapid clearance and low tumor absorption following intravenous administration in a mouse HER2-positive tumor model . Naproxen, a widely recognized nonsteroidal anti-inflammatory drug (NSAID), has recently garnered attention for its potential anticancer properties, as evidenced by its efficacy as a COX-2 inhibitor in clinical trials. − Our previous study proved that a combination of naproxen with nanoparticles results in better activity regarding the treatment of several diseases. − Despite these promising properties, there is limited research on the kinetic release model that typically occurs when B-CDs are combined with anticancer medications, both in vitro and in vivo. Consequently, it is crucial to evaluate the significance of drug release studies as a continuation of the efficacy of B-CDs therapy.…”