Self-Assembly Mediated Platform for Rapid and Facile Preparation of Peptide-Functionalized Nanoparticles with High Stability

We recently reported a two-component self-assembling system, where the core of nanoparticles (NPs) was first assembled by a simple triskelion Fmoc-conjugate (FTAEA) and then stabilized by an oligopeptide, Fmoc-FY. Here we showed that the two-component NPs were stable upon heating, incubation, and dilution. We expanded the oligopeptides suitable for stabilization and therefore allowed peptides to serve the dual role of stabilization and functionalization. Twelve molecules were systematically designed and tested to define the design criteria of oligopeptide stabilizers, which are summarized as follows: 1) carrying Fmoc headgroup to match with the aromatic groups on the NP core, 2) restricting the first amino acid to those with self-interacting side chains, and 3) the net charge of the hydrophilic oligopeptide sequence being negative. To validate these criteria, we designed two bioactive peptides, Fmoc-FC and Fmoc-FRGD, which were demonstrated to be capable of stabilizing FTAEA NPs. The bioactivity of the peptide was illustrated with Nile red-loaded Fmoc-FRGD stabilized NPs of around 70 nm in diameters. These NPs were differentially internalized by MDA-MB-435 human cancer cells compared to NPs stabilized with the scrambled sequence, Fmoc-FRDG. Our results here showed that the stepwise aromatic-driven self-assembly provided a facile and versatile approach to construct functionalized and bioactive NPs, which are expected to find applications in drug delivery and bioimaging

Self-Assembly Mediated Platform for Rapid and Facile Preparation of Peptide-Functionalized Nanoparticles with High Stability

We recently reported a two-component self-assembling system, where the core of nanoparticles (NPs) was first assembled by a simple triskelion Fmoc-conjugate (FTAEA) and then stabilized by an oligopeptide, Fmoc-FY. Here we showed that the two-component NPs were stable upon heating, incubation, and dilution. We expanded the oligopeptides suitable for stabilization and therefore allowed peptides to serve the dual role of stabilization and functionalization. Twelve molecules were systematically designed and tested to define the design criteria of oligopeptide stabilizers, which are summarized as follows: 1) carrying Fmoc headgroup to match with the aromatic groups on the NP core, 2) restricting the first amino acid to those with self-interacting side chains, and 3) the net charge of the hydrophilic oligopeptide sequence being negative. To validate these criteria, we designed two bioactive peptides, Fmoc-FC and Fmoc-FRGD, which were demonstrated to be capable of stabilizing FTAEA NPs. The bioactivity of the peptide was illustrated with Nile red-loaded Fmoc-FRGD stabilized NPs of around 70 nm in diameters. These NPs were differentially internalized by MDA-MB-435 human cancer cells compared to NPs stabilized with the scrambled sequence, Fmoc-FRDG. Our results here showed that the stepwise aromatic-driven self-assembly provided a facile and versatile approach to construct functionalized and bioactive NPs, which are expected to find applications in drug delivery and bioimaging

Additional file 1 of Atrial fibrillation is not an independent determinant of 28-day mortality among critically III sepsis patients

Supplementary Material

A Meta-Analysis of the Association between the hOGG1 Ser326Cys Polymorphism and the Risk of Esophageal Squamous Cell Carcinoma

<div><p>Background</p><p>Genetic polymorphism of human 8-oxoguanine glycosylase 1 (hOGG1) Ser326Cys (rs1052133) has been implicated in the risk of Esophageal Squamous Cell Carcinoma (ESCC). However, the published findings are inconsistent. We therefore performed a meta-analysis to derive a more precise estimation of the association between the hOGG1 Ser326Cys polymorphism and ESCC risk.</p><p>Methodology/Principal Findings</p><p>A comprehensive search was conducted to identify eligible studies of hOGG1 Ser326Cys polymorphism and the risk of the ESCC. Three English and two Chinese databases were used, and ten published case-control studies, including 1987 cases and 2926 controls were identified. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the association in the dominant and recessive model. Pearson correlation coefficient (PCC) and standard error (SE) were used to assess the number of Cys allele and ESCC risk in the additive model. Overall, significant associations between the hOGG1 Ser326Cys polymorphism and ESCC risk were found in the recessive model: OR = 1.37 (95% CI: 1.06–1.76, p = 0.02). We also observed significant associations in the Caucasian, Chinese language, population based control and tissue subgroups. In the additive model, positive correlation was found between the number of Cys allele and the risk of ESCC in overall studies (PCC = 0.109, SE = 0.046, p = 0.02), Caucasian subgroup and population subgroup. Funnel plot and Egger's test indicate there was no publication bias in this meta-analysis.</p><p>Conclusion</p><p>Under the published data, the hOGG1 Ser326Cys polymorphism is associated with ESCC risk in the recessive and additive model. Compared with the Ser/Ser and Ser/Cys genotype, Cys/Cys genotype might contribute to increased risk of ESCC. And the risk of ESCC is positively correlated with the number of Cys allele. A better case-control matched study should be designed in order to provide a more precise estimation.</p></div

Expression of miR-194-5p, miR-192-5p, and miR-215-5p in human colon cell lines.

<p>The level of expression is given in sequence counts per million.</p

Expression of miRNA precursor and its major mature form in 15 mouse tissues.

<p>A heat map was constructed using GenePattern software based on the normalized miRNA reads. Heat maps showed precursors and major forms to have similar patterns of expression.</p

Begg’s funnel plot with 95% confidence limits (CIs) of publication bias test.

<p>(A). recessive model; (B). dominant model.</p

Tissue coexpression score of miR-194-5p/miR-215-5p and miR-194-5p/miR-192-5p.

<p>The coexpression score was zero for all miRNA with no reads.</p

Potential HNF1 and HNF4 binding site in the promoters of pri-miR-194-1/miR-215 and miR-194-2/miR-192 genes in different species.

<p>Transcription binding sites were predicted using Motif-based sequence analysis tools.</p

Reads per million of miR-194-5p, miR-192-5p, and miR-215-5p in human colon cell lines.

<p>Reads per million of miR-194-5p, miR-192-5p, and miR-215-5p in human colon cell lines.</p