Nanomedical solutions to overcome Multi Drug Resistance (MDR) Ommolbanin Shahraki*1,2, Najmeh. Edraki2, Mehdi. Khoshnevis zadeh1,2, Omid.R. firuzi2, Ramin. Miri1,2, sara ranjbar1,2, Aida Iraji 1,3 1 Medicinal and Natural Products Chemistry Research Center, Shiraz, Iran 2 Department of Medicinal Chemistry, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran 3 Central laboratory, Shiraz University of Medical Science, Shiraz, Iran
[email protected] Cancer cell resistance is considered to be one of the major reasons for failure of chemotherapy for the majority of cancer patients. Some tumors are intrinsically resistant to treatment whereas others acquire resistance with exposure to structurally unrelated drugs. This phenomenon, multi-drug resistance (MDR) is the result of some mechanisms such as overexpression of membrane bound proteins that efflux drugs from the cells, thus decreasing the intracellular concentration of the drugs. P-glycoprotein, a member of the highly conserved superfamily of ATP-binding cassette (ABC) transporter proteins, is an important protein linked to MDR associated with a variety of cancers. Over the years, many different strategies have been employed to overcome multidrug resistance. most of these attempts have been unsuccessful, due to low selectivity, inherent toxicity and pharmacokinetic interactions with anticancer drugs. We want to focus on nanomedicines, which have also been extensively evaluated to overcome MDR in the last two to three decades, given their prolonged circulation properties and their ability to accumulate in tumors via enhanced permeability and retention. We will outline several prototypic strategies for employing nanomedicines to tackle MDR, including the use of carrier materials with intrinsic anti-resistance properties, the use of materials modifying the mode of cellular uptake of chemotherapeutic drugs, and the (co-) formulation of chemotherapeutic drugs together with low- and high-molecular-weight MDR inhibitors within a single drug delivery system. the insights obtained and the progress made strongly suggest that nanomedicine formulations hold significant potential for improving the treatment of multidrug-resistant malignancies. key words: P-glycoprotein, MDR, nanomedicine, ATP-binding cassette (ABC)
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