Different strategies to increase doxorubicin efficacy in erug resistant cancer cells based on physical, natural and pharmacological approaches / Gamal Eldein Fathy Abdellatef Abdelrahman ; Supervised Sohair Ramadan Fahmy , Chiara Riganti , Mohamed Assem Said Marie

Thesis (Ph.D.) - Cairo University - Faculty of Science - Department of Zoology

The resistance of cancer cells to a broad variety of anticancer drugs is known as multidrug resistance (MDR), which is a critical hindrance to the success of cancer chemotherapy and leads to tumor progression. It affects patients with hematological and solid tumors including breast and skin cancers.The main responsible for MDR phenotype are ATP Binding Cassette (ABC) transporters, plasma-membrane associated transporters that efflux multiple drugs outside the cells, limiting their intracellular accumulation and cytotoxicity.The main ABC transporter related to MDR is P-glycoprotein (P-gp). In this Thesis, three alternative approaches were investigated to inhibit P-gp in an effective and safe way: i) the use of photodynamic tools, i.e.molecules able to release a chemotherapeutic drug{u2013}doxorubicin{u2013}and a P-gp inhibitor{u2013}nitric oxide (NO){u2013}only if irradiated with proper wavelengths within tumor cells; ii) the use of natural products, with poor toxicity on nontransformed cells and high selectivity for P-gp overexpressing cells; iii) the use of a nanotechnological approaches, based on the co-administration of doxorubicin and a natural chemosensitizing product {u2013} curcumin {u2013} loaded in biocompatible solid lipid nanoparticles (SLN)

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