Researchers in this study developed a quantum dot-based drug delivery system that allowed anti-MDR1 siRNA and doxorubicin incorporation to two cadmium-selenium/zinc-selenium quantum dots that were eventually functionalized by β-cyclodextrin coupling to L-arginine or L-histamine [81]. Following deployment

of these dual loaded quantum dots in the HeLa cervical cancer cell line model, elevated accumulation of doxorubicin within the tumour cells was denoted, together with a marked reduction in MDR1 and P-gp expression on analysis by reverse transcription real time quantitative polymerase Inhibitors,research,lifescience,medical chain reaction and western blotting [81]. In line with magnetic and gold nanoparticle platforms, quantum dots rely mainly on the endosomal method of tumour cellular uptake and therefore the drug efflux pump system is bypassed, with consequent reduction in Inhibitors,research,lifescience,medical MDR properties by the tumour cells [82]. Finally, the additional benefit of utilizing quantum dots as a drug delivery system is their capacity to be tracked in real time within specific areas of the target cells, due

to their intrinsic fluorescence properties [81]. Apart from cell line studies, researchers have also looked into the BI 6727 order feasibility of implementing nanoparticle-based drug delivery systems within in vivo models [108]. The study by Milane et al. [108] investigated the efficacy Inhibitors,research,lifescience,medical of utilising a EGFR-targeting polymer blend nanoparticles, loaded

with paclitaxel and the mitochondrial hexokinase 2 inhibitor lonidamine. The nanoparticle polymer blend consisted of 70% polycaprolactone (PCL) incorporating a PLGA-polyethylene glycol-EGFR specific peptide that helped Inhibitors,research,lifescience,medical enable nanoparticle active targeting efficiency [108]. Following nanoparticle development, four groups of orthotopic MDR breast cancer murine models (MDA-MB-231 in nude mice) were treated with free paclitaxel, free lonidamine, free paclitaxel/lonidamine combination, or nanoparticle Inhibitors,research,lifescience,medical complexes containing paclitaxel/lonidamine combination [108]. The degree of toxicity of such treatments was also monitored through body weight change measurements, liver enzyme plasma levels, and white blood cell/platelet counts, together with H & E staining of tumour sections was carried Phosphoprotein phosphatase out [108]. Tumour weight and other clinical parameters such as MDR protein marker (P-gp, Hypoxia Inducible factor α, Hexokinase 2, EGFR, Stem Cell factor) were observed over the course of 28 days after-treatment [108]. Following this 28-day period, the results demonstrated that only the murine model sample group exposed to the nanoparticle-based paclitaxel/lonidamine combination treatment was the only group to experience statistically significant tumour volume and density reduction, together with overall alteration of the MDR phenotype [108].