Synthesis of cancer cell membrane coated magnetic iron oxide nanoparticles and investigation of cytotoxic efficacy in glioblastoma treatment

The most prevalent and deadly primary brain cancer in adults is called glioblastoma (GBM), In cases of GBM, chemotherapy is the most often used treatment after surgical resection. However, the clinical effectiveness of drug therapy in GBM is not very satisfactory. Efficient drug delivery for GBM is largely restricted by poor physicochemical properties, low targeting ability of therapeutic molecules, and the presence of both the BBB and the blood-brain tumor barrier (BBTB). Therefore, there is an urgent need to develop new therapeutic platform that overcome physiological and pathological barriers in the treatment of GBM. Scientists are focused on developing new therapeutic approaches such as cell membrane (CM) camouflage to increase the biocompatibility and active targeting ability of nanocarrier systems. The use of cell membrane-based nanoparticles is becoming an effective approach to deliver a wide range of functionality to conventional applications. Obtaining natural biomimetic nanostructures by combining cell membranes with nanoparticle structures is a developing field of research. Coating cell membranes on nanoparticles provides an effective biointerface. Long-term circulation and active targeting in the body can be accomplished by creating these nanocarriers with surfaces that accurately mimic complicated biological functions. These surfaces mostly originate from the cell membrane and copy the characteristics of the parent cell. In this study, it was aimed to investigate the effect of the synthesized biomimetic nanoplatform in the treatment of GBM. First, magnetic iron oxide particles were synthesized by co-precipitation method. Size distribution and zeta potential of magnetic iron oxide particles were analyzed via DLS. Membrane fragments were isolated from the U87-MG cell line from glioblastoma astrocytomas isolated from human brain, and membrane proteins were detected by western blotting. Afterwards, the biomimetic nano platform (Fe3O4@CM) were assembled by coextrusion method. The copolymers containing tertiary butoxide-protected lysine methacrylate (tBoc2LysMA) temozolomide methacrylate (TMZMA) and 2-hydroxy-ethyl methacrylate (HEMA) units were synthesized via RAFT polymerization. Then, tBoc protecting groups were removed via acidic hydrolysis reaction. Polymers were characterized by nuclear magnetic resonance spectroscopy, gel permeation chromatography and Fourier transform infrared spectroscopy (1H NMR, GPC and FTIR) analyses. The size and morphology of the biomimetic nanoplarforms were characterized using TEM analysis. Therapeutic effect of the obtained nanoplatforms against U87-MG glioblastoma cancer cell and CCD-1079Sk healthy human fibroblast cell line as a control cell line 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test was evaluated for cytotoxicity.