Nanomedical solutions to overcome Multi Drug Resistance(MDR)

Cancer cell resistance is considered to be one of the major reasons for failure ofchemotherapy for the majority of cancer patients. Some tumors are intrinsically resistant totreatment whereas others acquire resistance with exposure to structurally unrelated drugs.This phenomenon, multi-drug resistance (MDR) is the result of some mechanisms such asoverexpression of membrane bound proteins that efflux drugs from the cells, thus decreasingthe intracellular concentration of the drugs. P-glycoprotein, a member of the highly conservedsuperfamily of ATP-binding cassette (ABC) transporter proteins, is an important proteinlinked to MDR associated with a variety of cancers.Over the years, many different strategies have been employed to overcome multidrugresistance. most of these attempts have been unsuccessful, due to low selectivity, inherenttoxicity and pharmacokinetic interactions with anticancer drugs. We want to focus onnanomedicines, which have also been extensively evaluated to overcome MDR in the last twoto three decades, given their prolonged circulation properties and their ability to accumulatein 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 ofmaterials modifying the mode of cellular uptake of chemotherapeutic drugs, and the (co-)formulation of chemotherapeutic drugs together with low- and high-molecular-weight MDRinhibitors within a single drug delivery system.the insights obtained and the progress made strongly suggest that nanomedicine formulationshold significant potential for improving the treatment of multidrug-resistant malignancies.

کلیدواژه ها:

P-glycoprotein ، MDR ، nanomedicine ، ATP-binding cassette (ABC)