Copper oxide nanoparticles as delivery vehicles for different Pt(II)-drugs: experimental and theoretical evaluation.

Chemotherapy is a key element in cancer treatment. The first drugs to be clinically used for this purpose were platinum(II) complexes and even today they are highly effective in the treatment of the disease. However, side effects, resulting from their use, limit their clinical usefulness. Furthermore, if administered intravenously into the circulation, platinum(II)-based anticancer medications may cause adverse effects due to interactions with molecules found in human bodies, thus preventing them to reach the final target. Stomach secretions can also destroy them. As a result, their absorption might be restricted, rendering oral delivery ineffective. Over the years, several methodologies were developed to overcome the limits associated with the use of the platinum(II) drugs, including their targeted delivery. In this context, our study proposes copper(II) oxide nanoparticles (CuO NPS) as a promising and excellent carrier of platinum(II)-based anticancer drugs. In this work, we examined the loading efficiency of cisplatin, oxaliplatin and nedaplatin on the surface of CuO nanoparticles by using experimental techniques such as UV-visible spectroscopy, FTIR spectroscopy, the BET method, and XRD, and theoretical ones based on DFT calculations under periodic boundary conditions (PBC). UV-vis spectroscopy determined that cisplatin had the highest entrapment efficiency and loading capacity compared to the other drugs, with 52% entrapment efficacy and an adsorption capacity of 949 mg g, indicating a stronger binding with CuO nanoparticles. The experimental results are consistent with DFT simulations indicating that Pt(II)-drugs exhibit favorable adsorption on CuO (111) surfaces, particularly when the Pt(II)-drug is cisplatin. The most stable configurations indicate that cisplatin, nedaplatin, and oxaliplatin prefer to coordinate with the surface tri-coordinated Cu. However, cisplatin has the most intense contact with the copper oxide surface, with an adsorption energy () of -3.0 eV. Both experimental and theoretical results highlight that CuO nanoparticles are excellent Pt(II) anticancer drug carriers, especially in the case of cisplatin, which undergoes strong interactions with the support, necessary for the delivery phase, and easy desorption, important in the antitumor action phase of the drug.