Mar Creixell1, Nicholas A Peppas2. 1. Department of Chemical Engineering, C0400, The University of Texas at Austin, Austin, TX 78712, USA. 2. Department of Chemical Engineering, C0400, The University of Texas at Austin, Austin, TX 78712, USA ; Department of Biomedical Engineering, C0800, The University of Texas at Austin, Austin, TX 78712, USA ; College of Pharmacy, C0400, The University of Texas at Austin, Austin, TX 78712, USA.
Abstract
There are two main mechanisms by which cells become multidrug resistant (MDR): by increasing drug efflux pumps on the cell membrane and by increasing anti-apoptotic pathways. The use of nanotechnology to develop nanodelivery systems has allowed researchers to overcome limitations of antineoplastic drugs by increasing the solubility of the drug and decreasing the toxicity to healthy tissues. By encapsulating drugs into nanoparticles that bypass the efflux pumps, drug efflux is reduced, hence increasing the intracellular concentration of the drug. siRNA has the ability to disrupt cellular pathways by knocking down genes, opening the door to down regulating anti-apoptotic pathways. The use of nanocarriers to deliver siRNA, prevents both renal clearance and RNase degradation by protecting siRNA chains, increasing their half life in blood. It has been suggested that co-delivering drugs and siRNA together in the same delivery system would be more effective in overcoming resistance of cancer cells than co-treatment of cancer cells with delivery systems carrying either siRNA or drugs. In this study we discuss the progress of nanoscale co-delivery systems in overcoming multidrug cancer resistance.
There are two main mechanisms by which cells become multidrug resistant (MDR): by increasing drug efflux pumps on the cell membrane and by increasing anti-apoptotic pathways. The use of nanotechnology to develop nanodelivery systems has allowed researchers to overcome limitations of antineoplastic drugs by increasing the solubility of the drug and decreasing the n class="Disease">toxicity to healthy tissues. By enpan>capsulating drugs into nanpan>oparticles that bypass the efflux pumps, drug efflux is reduced, henpan>ce increasing the intracellular conpan>cenpan>trationpan> of the drug. siRNA has the ability to disrupt cellular pathways by knpan>ocking downpan> genpan>es, openpan>ing the door to downpan> regulating anpan>ti-apoptotic pathways. The use of nanpan>ocarriers to deliver siRNA, prevenpan>ts both renpan>al clearanpan>ce anpan>d RNase degrpan> class="Disease">adation by protecting siRNA chains, increasing their half life in blood. It has been suggested that co-delivering drugs and siRNA together in the same delivery system would be more effective in overcoming resistance of cancer cells than co-treatment of cancer cells with delivery systems carrying either siRNA or drugs. In this study we discuss the progress of nanoscale co-delivery systems in overcoming multidrug cancer resistance.
Entities:
Keywords:
Cancer therapy; Co-delivery; Doxorubicin; Multi drug resistance (MDR); Nanoparticles; siRNA
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