Determinants of gold nanoparticle interactions with Proteins: Off-Target effect study.

Photothermal therapy is one of the promising approaches toward cancer treatment. To date, several compounds have been developed for this application, among which nanoparticles are attracting ever-increasing attention. One of the obstacles in developing efficient photothermal nanoparticle agents is their off-target effect which is mainly mediated via non-specific interactions with proteins. Such interaction not only reduces the bioavailability of the agent but also will cause protein aggregation that can be lethal. So, gaining knowledge on the mechanisms mediating such interactions will facilitate development of more effective agents. Our last studies showed the mechanism of action of two modified gold nanoparticles, folic acid functionalized gold nanoparticles (FA-AuNPs) and gold shelled Fe3O4 nanoparticles (AuFeNPs), as photothermal agents. In the current work, we focus on the interaction of these two NPs with human serum albumin (HSA) and human hemoglobin (Hb) as model proteins. The complex formation between NPs and proteins was investigated by fluorescence spectroscopy, dynamic light scattering and circular dichroism. Our data distinguishes the very distinct mode of interaction of charged and neutral NPs with proteins. While the interaction of neutral AuFeNP to proteins is protein dependent, charged nanoparticles FA-AuNP interact indistinguishably with all proteins via electrostatic interactions. Moreover, complexes obtained from FA-AuNPs with proteins are more stable than that of AuFeNP. However, the secondary structure content of proteins in the presence of NPs indicates the insignificant effect of NPs on the secondary structure of these proteins. Our data propose that the charge functionalization of the NPs is an effective way for modulating the interaction of nanoparticles with proteins.

Tinnitus: an epidemiologic study in Iranian population.

A wide range of population, 4% to 30%, suffers from tinnitus that is defined as perception of sound without apparent acoustic stimulus. We conducted the present study to determine the prevalence of tinnitus in Iranian population; Tehran province. This cross-sectional study was conducted from January 2009 to December 2009, recruiting 3207 individuals (age range, 7-98) who were residing in Tehran province, Iran. Participants were asked to fill two questionnaires; the validated Persian version of Tinnitus Questionnaire (TQ) and another one that was specifically designed for this study. Prevalence of tinnitus and its association factors were evaluated. 3207 participants enrolled into our study comprising 1429 (44.7%) male and 1765 (55.3%) female with mean age of 55.01±17.85. Of total of 3207 participants, 146 (4.6%) had tinnitus consisting of 80 male (54.8%) and 66 (45.2%) female participants. It showed a rising trend with increasing age that was especially significant after the sixth decade of life (P=0.001). The analysis showed mean TQ global score of 35.96±25.52 that was significantly different between male and female participants (P=0.051) and had no significant correlation with increasing age (Spearman's r=0.1, P=0.10). The tinnitus intensity was moderate to very severe in 95 (56.1%) of the participants. Its severity level was not significantly different between men and women (P=0.09). Tinnitus intensity had no significant association with increasing age (Spearman's r=0.1, P=0.31). Patients with higher TQ global score had higher tinnitus intensities (P=0.001). The annoyance level was significantly different between men and women (P=0.04) and its impact on the participants daily routine functions were significantly higher in men (P=0.003). Given the results of the study, demonstrating that prevalence of tinnitus in Iranian population (Tehran province) was lower than the other countries and had a direct correlation with increasing age only after the sixth decade. TQ global score had significant correlation with tinnitus intensity, annoyance and impact on the participants' daily routine functions. However, none of the above had correlation with increasing age. Tinnitus TQ global score and intensity were not different between men and women; however annoyance of tinnitus and its impact on participants' daily routine functions were significantly higher in men.