Copper Oxide as an Anti-Neoplastic Agent for Endometrial Carcinoma

Carboplatin, a platinum-based drug, is commonly administered to treat endometrial cancer; however, efficacy is limited by chemotherapeutic resistance. Chemotherapeutic resistance is one of the greatest difficulties to overcome in cancer therapy, resulting in a vital demand for new anti-cancer drugs and drug-delivery devices. In addition to chemotherapeutic resistance, unequitable access to treatment options for endometrial cancer patients demonstrates the need for a non-invasive form of endometrial cancer therapy. A proposed solution to these challenges involves using copper oxide nanoparticles as an alternative metal to platinum-based drugs in a biodegradable polymeric nanoparticle to combat the issues of chemotherapeutic resistance and unequitable access to care.

Copper oxide nanoparticles pose a potential as an anti-cancerous compound due to Cu²⁺ ions demonstrating the ability to induce reactive oxygen species (ROS) leading to double stranded DNA breaks ultimately resulting in cell death. Polycaprolactone (PCL, Sigma) was used to encapsulate copper (II) oxide nanoparticles (CuO NPs, Sigma) in a polymeric nanoparticle using the double emulsion solvent evaporation technique with nanoprecipitation. Cell viability after 24 hours of treatment with 60-minute sonicated CuO NPs was assessed through MTT assays.

AN3CA, HEK293, A549, HEC-1A, KLE, and Ishikawa cell lines all showed sensitivity to CuO NPs; however, each cell line experienced a different response to CuO NP treatment. HEK293 cells showed a low sensitivity to CuO NPs with >50% viability at 100 µg/mL. KLE MTT assay results did not show a direct correlation between cell viability and CuO NP concentration. Ishikawa and A549 cells demonstrated a negative correlation between cell viability and concentration.

Compared to sonicating for 30 minutes and no sonication, CuO NPs sonicated for 60 minutes in a water bath resulted in effective dispersion and reduced hydrodynamic size. Sonication resulted in minor changes in zeta potential of CuO NPs in PBS. Zeta potential measurements of CuO-PEI nanoplexes were similar across three different wt% PEI used to create the complexes. Additionally, the zeta potential measurements of CuO NPs, PEI, and CuO-PEI nanoplexes were all different, indicating that CuO-PEI complexes were being formed. PCL shell CuO-PEI core in water nanoparticles were successfully synthesized using the proposed synthesis method. SEM imaging revealed that particle diameter was greater than 1 µm. MTT assay results confirmed that CuO NPs result in effective cell death in all human cell lines tested at or below 100 µg/mL. All cell lines showed differing trends and results for viability when treated with CuO NPs.