Spectroscopic and In Silico Characterization of Irinotecan-Loaded Nanoparticles: In Vitro Evaluation for Breast Cancer Treatment

Abstract

Cancer has always posed a significant threat to human health. Chemotherapy agents used in cancer treatment can also damage normal cells. The area that attracts the most attention today is the transport of chemotherapeutic drugs and the reduction of their side effects by nanotechnological methods. While increasing the stability of drugs or proteins by using nanoparticles with nanotechnology methods, controlled drug release in the target region is also aimed. Our study, it is aimed to determine the effect of iron oxide nanoparticles coated with poly-3-hydroxybutyrate (PHB) loaded with Irinotecan, an anticancer agent, on cancerous cells. In our study, Irinotecan anticancer agent and PHB molecule drawings, molecular electrostatic potential maps, and Mulliken charges of atoms were calculated with the Gaussian 09 program, and theoretical IR spectra were drawn with the Origin85 program. Before the calculation to be made in the Gaussian 09 package program, the GaussView 5.0 package program, which serves as a utility for this program, is used. The GaussView 5.0 program makes a 3-dimensional design of a molecule and provides a visual description of the molecule's properties. At the same time, the GaussView 5.0 program visualizes the calculation outputs made by the Gaussian 09 program. The geometrical structure parameters of Irinotecan anticancer agent and PHB molecule were calculated theoretically by considering the most stable structure of the molecules, such as bond length, bond angles and angle bending, binding energies. The drug-loaded nanoparticles were completed and calculated in BIODRAW and Gaussian programs, molecular docking and dynamic analysis was performed with anti-apoptotic proteins. At the same time PHB coated nanoparticles were in situ synthesized as nanocarrier systems and loaded with the drug Irinotecan. The drug loading capacity, drug release and stability of nanoparticle were analyzed. The cytotoxicity of nanoparticle, drug and drug loaded nanoparticles were tested by XTT analyses in vitro. We analyzed the 3D drawings of the PHB molecule and the cancer drug Irinotecan with the GaussView program and optimized it with the Gaussian 09 program. Then, we created molecular electrostatic potential maps with the GaussView program to determine the binding regions of these structures. In-vitro analysis, the IC50 was determined on breast cancer cells. In-silico analysis, molecular docking studies have been carried out on the different classes of Irinotecan, nanoparticles and Irinotecan loaded nanoparticles the target proteins. As a result of the analysis, the Irinotecan loaded PHB coated nanoparticles has been observed to be effective against cancer and likely to be a potential drug.