Date

2022-8-03

Author

Parsian, Maryam

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The development of new tissue culture models is needed in cancer research and personalized medicine to better predict patients' responses to treatment. Using live tumor cells as a testing platform for drug development and identifying optimal therapy is a promising strategy. We described a new tissue culture approach that combines a microfluidic chip with the micro-dissected breast cancer tumor slices. The tumors from MDA-MB-231, SKBR-3, and MCF-7 cell lines were created in CD1 nude mice cultured in this microfluidic chip as an ex vivo culture. 'Tumor-ona- chip' devices are suitable for precision medicine since the viability of tissue samples is maintained during the culture period by continuously feeding fresh media and eliminating metabolic wastes from the tissue. This microfluidic system allows living tumor tissue to be kept alive and tested in laboratory conditions for 96 hours. Traditional chemotherapy methods used in cancer treatment cause side effects and drug resistance, thus reducing treatment efficacy and success. Therefore, in recent years, efforts have been focused on drug targeting and controlled drug release systems in cancer treatment. Nano-sized iron oxide particles have gained importance in drug targeting and controlled release due to their targetability under a magnetic field. Palbociclib (Ibrance®) is a chemotherapeutic agent used to treat ER-positive and HER-negative metastatic breast cancer. Synthesis of PAMAM dendrimer coated magnetic nanoparticles (DcMNPs) was followed by conjugation of Palbociclib to the nanoparticles and characterization. The cytotoxicity of Palbociclib and Palbociclib conjugated magnetic nanoparticles were examined and compared on the breast cancer cells in the 2D, 3D (hanging droplet method, and ex-vivo cultures. The confocal microscopy images revealed bare magnetic nanoparticles' uptake and internalization differences in three cultural methods. These analyses have shown that nanoparticles can be targeted in the presence of magnets and can penetrate into the interior parts in 3D and ex vivo cultures. It is known that the cells grown in 3D culture have different morphology and gene expression profiles when compared to cells in 2D culture. The changes in the expression levels of genes related to breast cancer development after applying Palbociclib conjugated DcMNP or free Palbociclib to 2D, 3D, and ex vivo cultures were investigated by the qRT-PCR method. Studies in 3D and ex-vivo environments will give rise to the development of rapid diagnostic and targeted personalized chemotherapy methods when performed with tumor specimens taken from the patients.

Subject Keywords

Ex-vivo culture, Microfluidics, 3D culture, Magnetic PAMAM dendrimer, Palbociclib

URI

https://hdl.handle.net/11511/98655

Collections

Graduate School of Natural and Applied Sciences, Thesis