Design of dendrimer-based nanocarrier system for targeted drug delivery to deep-sitted tumor cells :Sh in the breast cancer spheroid model MDA-MB-231 .

Abstract

Breast cancer is second common cancer across the world which counts predominant in modern countries And the use of chemotherapy is used as a common method for treatment, but it is not a responsive treatment, so the focus is on the tumor microenvironment to improve the penetration of nanoparticles into the center of the tumor, Therefore, a novel multifunctional hypoxia-induced size-shrinkable the nanoparticle has been designed to increase the penetration of drugs Marerials and method Doxorubicin is first physically loaded into 5th generation PAMAM dendrimers. The dendrimers are then crosslinked with a hypoxic linker, and a peg layer is added to the dendrimer nanoparticles as a corona using the azo linker. In the following, the characterization of the dendrimer-based nanocarrier system is investigated using spectroscopic and microscopic techniques. The performance of drug release from nanoparticles with and without hypoxia linker in MDA-MB-23 breast cancer cells cultured as monolayer and spheroid will be investigated. The effectiveness of nanoparticles will be evaluated by cytotoxic tests and the expression of genes involved in hypoxia, apoptosis and macroscopic and microscopic changes in the size of spheroids. conclusion The results show that the active and targeted transfer of doxorubicin loaded with produced nanoparticles with the aim of reducing toxicity using (mPEG) and increasing the specific performance of nanoparticles using a linker sensitive to hypoxia (Azobenzene) shows the most efficiency for the treatment of breast cancer cells. Key word: Breast cancer, hypoxia, PAMAM G5, azobenzene, penetration, apoptosis