rs10490924 surrounding HTRA1/ARMS2 regulates the susceptibility of age-related macular degeneration.

Multiple studies have assessed the contribution of rs10490924 on chromosome 10q26 surrounding HTRA1/ARMS2 gene to age-related macular degeneration (AMD) risk. However, the causal allele at this locus is still inconclusive. In this meta-analysis, we systematically characterized the potential association between rs10490924 polymorphism and AMD risk. Data available from 12 case-control studies, including a total of 5244 cases and 2755 controls in three different ethnic populations, were used to evaluate the correlation between rs10490924 G/T polymorphism (Ala69Ser) and AMD risk. In overall populations, the results indicated the Ala69Ser polymorphism was significantly associated with AMD under allelic (OR = 0.35, 95% CI = 0.30-0.40), homozygous (OR = 0.12, 95%CI = 0.09-0.17), dominant (OR = 0.18, 95%CI = 0.14-0.24), recessive (OR = 0.33, 95%CI = 0.28-0.39), and heterozygous genetic models (OR = 0.26, 95% CI = 0.21-0.33). Similar results were observed in subgroup analysis. This meta-analysis suggests that rs10490924 (Ala69Ser) polymorphism was significantly associated with the susceptibility of AMD in all ethnicities, Ala69 carriers are resistant to AMD risk.

Dendrimer nanoclusters loaded with gold nanoparticles for enhanced tumor CT imaging and chemotherapy via an amplified EPR effect.

The design of efficient multifunctional nanomedicines to overcome adverse side effects within biological systems and to achieve desirable computed tomography (CT) imaging and therapeutics of tumors remains challenging. Herein, we report the design of multifunctional nanoclusters (NCs) based on generation 3 (G3) poly(amidoamine) (PAMAM) dendrimers. In brief, G3 dendrimers were crosslinked with 4,4'-dithiodibutryic acid (DA) to generate disulfide-bond-containing dendrimer nanoclusters (DNCs), functionalized with 1,3-propane sultone (1,3-PS) to be zwitterionic, in situ loaded with gold nanoparticles (Au NPs), and finally encapsulated with the drug doxorubicin (DOX). The designed DOX/Au@DNCs-PS possess a favorable colloidal stability with a hydrodynamic size of 249.4 nm, a redox-responsive drug release profile, and enhanced cellular uptake in vitro. We show that DOX/Au@DNCs-PS have a greater DOX penetration and growth inhibition of three-dimensional (3D) tumor spheroids than the single dendrimer counterpart in vitro. Furthermore, the developed Au@DNCs-PS enable a better Au-mediated X-ray attenuation property than the single dendrimer counterpart material. Likely due to the amplified enhanced permeability and retention (EPR) effect, the created Au@DNCs-PS and DOX/Au@DNCs-PS enable better CT imaging and chemotherapeutic effect of a mouse breast tumor model, respectively, than the single dendrimer counterparts. With its proven biocompatibility, the constructed formulation may hold promising potential for development for different cancer nanomedicine applications.