Therapeutic potential of glucose oxidase loaded mesoporous silica nanoparticles in ovarian cancer

Abstract

Ovarian cancer (OC) represents ones of the most dangerous malignancies of the female reproductive system, claiming the lives of thousands of women worldwide. Rapid disease progression and non-efficient treatments that cause systemic toxicity offer opportunities for innovative technology to address these issues. Glucose oxidase (GOx) is an enzyme that converts glucose into D-gluconic acid and hydrogen peroxide (H2O2), thus being used as a starvation strategy for cancer cells. However, systemic toxicity, inadequate stability, and immunogenicity hinder the application of GOx in cancer therapy. Nanotechnology surges as a strategy to improve therapeutic efficacy while minimizing side effects when used as drug delivery systems (DDS). Mesoporous silica nanoparticles (MSNs) serve as nanocarriers owing to their elevated loading capacity, facile functionalization, extensive surface area, and biocompatibility. This study seeks to examine the impact of GOx-loaded MSNs in OC by assessing cytotoxicity and differential expression of genes associated with carcinogenesis. The immobilization of GOx onto MSNS was conducted using 3-aminopropiltrietoxysilane (APTES) and glutaraldehyde (GTA). This approach yielded an immobilization percentage of 49.24%, accompanied by a reduction in enzymatic activity in the nanoformulation relative to the free enzyme. Techniques such as FTIR, DLS, SEM/EDX, XRD and BET were employed to characterize the MSNs before and after their immobilization with GOx. In vitro cytotoxicity and target gene expression were evaluated in the SKOV3 cell line. The IC50 values for free and immobilized GOx were found to be 60.77 ng/mL and 111.6 μg/mL, respectively. Moreover, a significant downregulation of the oncogene CTNNB1 was observed after 24 h of treatment with the nanoformulation. These findings represent the initial advancements in the application of GOx for ovarian cancer treatment.