“Manganese Extraction” Strategy Enables Tumor-Sensitive Biodegradability and Theranostics of Nanoparticles

Biodegradability of inorganic nanoparticles is one of the most critical issues in their further clinical translations. In this work, a novel “metal ion-doping” approach has been developed to endow inorganic mesoporous silica-based nanoparticles with tumor-sensitive biodegradation and theranostic functions, simply by topological transformation of mesoporous silica to metal-doped composite nanoformulations. “Manganese extraction” sensitive to tumor microenvironment was enabled in manganese-doped hollow mesoporous silica nanoparticles (designated as Mn-HMSNs) to fast promote the disintegration and biodegradation of Mn-HMSNs, further accelerating the breakage of Si–O–Si bonds within the framework. The fast biodegradation of Mn-HMSNs sensitive to mild acidic and reducing microenvironment of tumor resulted in much accelerated anticancer drug releasing and enhanced T₁-weighted magnetic resonance imaging of tumor. A high tumor-inhibition effect was simultaneously achieved by anticancer drug delivery mediated by PEGylated Mn-HMSNs, and the high biocompatibility of composite nanosystems was systematically demonstrated in vivo. This is the first demonstration of biodegradable inorganic mesoporous nanosystems with specific biodegradation behavior sensitive to tumor microenvironment, which also provides a feasible approach to realize the on-demand biodegradation of inorganic nanomaterials simply by “metal ion-doping” strategy, paving the way to solve the critical low-biodegradation issue of inorganic drug carriers

Vitamin D Receptor Gene FOKI Polymorphism Contributes to Increasing the Risk of HIV-Negative Tuberculosis: Evidence from a Meta-Analysis

<div><p>Background</p><p>Vitamin D receptor (VDR) gene <i>Fok</i>I polymorphism have been studied in relation to tuberculosis (TB) in many populations and provided inconsistent results. In this study, we carried out a meta-analysis to derive a more reliable assessment on <i>Fok</i>I polymorphism and the risk of HIV-negative TB.</p><p>Methods</p><p>The Embase, PubMed, and Cochrane Library databases were used to undertake a comprehensive systematic literature review of all current published VDR gene <i>FOKI</i> association studies aimed at the risk of TB up to June 30, 2015. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were used to measure the strength of the models.</p><p>Results</p><p>A total of 14 studies (1,668 cases and 1,893 controls) were retrieved in the meta-analysis. The pooled OR was 1.60 (95% = 1.28–1.97, <i>P</i><0.001; <i>I</i>^<i>2</i> = 29.5%, and <i>P</i> = 0.141 for heterogeneity) in the best genetic model (recessive model: ff vs. fF+FF). In the subgroup analysis by ethnicities, a significantly increased risk was found in the Asian group (OR = 1.82, 95% CI = 1.42–2.33, <i>P</i><0.001; <i>I</i>^<i>2</i> = 31.0%, and <i>P</i> = 0.150 for heterogeneity) in the recessive model. Similarly, significant associations were also found in the polymerase chain reaction-restriction fragment length polymorphism group, high-quality studies, and the population based or hospital based groups. Moderate heterogeneity was found in this study.</p><p>Conclusion</p><p>Our results suggested that VDR <i>Fok</i>I polymorphism contributes to increasing the risk of TB in HIV-negative individuals, especially in the Asian region. Further studies on this topic in other races are expected to be conducted in future.</p></div

Characteristics of studies included in the meta-analysis.

<p>PB, Population—based; HB, Hospital—based; PTB, pulmonary tuberculosis; MTB, meningeal tuberculosis; SSP-PCR, sequence specific primer-polymerase chain reaction; RFLP-PCR, polymerase chain reaction-restriction fragment length polymorphism; HWE, Hardy—Weinberg equilibrium in control population</p><p>Characteristics of studies included in the meta-analysis.</p

Scale for quality assessment.

<p>Scale for quality assessment.</p

Forest plot of VDR <i>Fok</i>I Polymorphism and HIV-negative TB risk in recessive model.

<p>Forest plot of VDR <i>Fok</i>I Polymorphism and HIV-negative TB risk in recessive model.</p

Flow diagram of included studies for this meta-analysis.

<p>Flow diagram of included studies for this meta-analysis.</p

Begg’s funnel plot for contrast in overall analysis in recessive model.

<p>Each point represents a separate study for the indicated association. Size graph symbol by weights. <i>Log[OR]</i> natural logarithm of OR. Horizontal line mean effect size.</p

Sensitivity analysis for VDR <i>Fok</i>I Polymorphism and HIV-negative TB risk in recessive model.

<p>This figure shows the influence of individual studies on the summary OR. The middle vertical axis indicates the overall OR and the two vertical axes indicate its 95% CI. Every hollow round indicates the pooled OR when the left study is omitted in this meta-analysis. The two ends of every broken line represent the 95% CI.</p

Hollow Mesoporous Organosilica Nanoparticles: A Generic Intelligent Framework-Hybridization Approach for Biomedicine

Chemical construction of molecularly organic–inorganic hybrid hollow mesoporous organosilica nanoparticles (HMONs) with silsesquioxane framework is expected to substantially improve their therapeutic performance and enhance the biological effects beneficial for biomedicine. In this work, we report on a simple, controllable, and versatile chemical homology principle to synthesize multiple-hybridized HMONs with varied functional organic groups homogeneously incorporated into the framework (up to quintuple hybridizations). As a paradigm, the hybridization of physiologically active thioether groups with triple distinctive disulfide bonds can endow HMONs with unique intrinsic reducing/acidic- and external high intensity focused ultrasound (HIFU)-responsive drug-releasing performances, improved biological effects (e.g., lowered hemolytic effect and improved histocompatibility), and enhanced ultrasonography behavior. The doxorubicin-loaded HMONs with concurrent thioether and phenylene hybridization exhibit drastically enhanced therapeutic efficiency against cancer growth and metastasis, as demonstrated both <i>in vitro</i> and <i>in vivo</i>