Here, we tested whether conjugation of saporin with QDs could result in BI 6727 similar microglia specific cell loss. To confirm the conjugation of saporin with QDs, XPS was used to compare the chemical composition of unconjugated and saporin conjugated QDs adsorbed on a silicon surface. While negligible carbon was present on the silicon surface due to impurities, the carbon composi tion increased for the silicon surface adsorbed with QDs. There was a further increase in carbon for surface adsorbed with saporin conjugated QDs, consistent with the presence of streptavidin and saporin, which are com posed predominantly of carbon. This increase was associated with a decrease in oxygen composition on the surfaces. Moreover, there was a decrease in the elements present in QDs, namely Se, S, Cd and Zn after conjugation with saporin, further suggesting successful conjugation.

High resolution C1s scans were taken to further support the presence of saporin on the QDs. The major hydrocarbon peak was at 285. 2 eV. A binding energy at 286. 8 eV is assigned to amines, and a binding energy at 288. 0 eV is assigned to amide functional groups. For the silicon surface, there was only one peak Inhibitors,Modulators,Libraries at 285. 2 eV. For QDs, apart from the hydrocarbon peak at 285. 2 eV, peaks for amine and amide were also present. After saporin conjugation, the intensities of the amine and amide peaks increased, as shown in the deconvolution of high resolu tion C1s spectra into individual peaks. The decreased contribution of the hydrocarbon peak at 285.

2 eV and the subsequent increase in amide and amine peaks at other Inhibitors,Modulators,Libraries binding energies reflect the successful conjugation of the QD surface with saporin. We then applied QDs conjugated with saporin to pri mary cultures for 2 days and quantified microglia after the treatment by Iba 1 expression. Application of QD Sap caused a marked reduction of microglia labeled with an antibody against Iba 1, without affecting the Inhibitors,Modulators,Libraries number or morphology of neurons or astroglia. Treatment with unconjugated QDs or saporin alone did not significantly affect the number of microglia compared with untreated control. Next, we tested the effects of QD Sap induced micro glial ablation on Ab toxicity in mixed cortical cultures. Depletion of microglia with QD Sap significantly increased the number of MAP2 positive neurons that survived Ab1 42 treatment.

Application of QDs or saporin alone had no effects. Thus, neurons could be preserved in this neurodegenerative disease model through the selective targeting of microglia Inhibitors,Modulators,Libraries with modified QDs. Discussion Our study shows that QDs are preferentially taken up by microglia in mixed cortical cultures and in brain. We further showed that the major cellular uptake pathway of QDs in microglia is clathrin Inhibitors,Modulators,Libraries mediated endocytosis involving the microglia specific receptors www.selleckchem.com/products/CHIR-258.html MSR 1 and mannose receptor.