Hybrid nanoreservoirs based on dextran-capped dendritic mesoporous silica nanoparticles for CD133-targeted drug delivery

In this study, the chemical features of dendritic mesoporous silica nanoparticles (DMSNs) provided the opportunity to design a nanostructure with the capability to intelligently transport the payload to the tumor cells. In this regard, doxorubicin (DOX)-encapsulated DMSNs was electrostatically surface-coated with polycarboxylic acid dextran (PCAD) to provide biocompatible dextran-capped DMSNs (PCAD-DMSN@DOX) with controlled pH-dependent drug release. Moreover, a RNA aptamer against a cancer stem cell (CSC) marker, CD133 was covalently attached to the carboxyl groups of DEX to produce a CD133-PCAD-DMSN@DOX. Then, the fabricated nanosystem was utilized to efficiently deliver DOX to CD133+ colorectal cancer cells (HT29). The in vitro evaluation in terms of cellular uptake and cytotoxicity demonstrated that the CD133-PCAD-DMSN@DOX specifically targets HT29 as a CD133 overexpressed cancer cells confirmed by flow cytometry and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay. The potentially promising intelligent-targeted platform suggests that targeted dextran-capped DMSNs may find impressive application in cancer therapy.     

Activation of subtilisin Carlsberg in hexane by lyophilization in the presence of fumed silica

Subtilisin Carlsberg (SC) was lyophilized from an aqueous buffer solution containing different amounts of unmodified commercial fumed silica. The activity of the enzyme/fumed silica preparation in hexane was compared to pure freeze-dried enzyme, and to a freeze-dried preparation reported in the literature with potassium chloride as additive. A sharp increase in enzyme activity was found to correlate with an increasing amount of fumed silica added to the enzyme solution prior to freeze-drying. A weight-ratio of 98.5 wt.% fumed silica relative to the mass of the final enzyme/fumed silica preparation led to about 130-fold increased activity of SC in hexane (when compared to pure lyophilized SC in hexane). This is about twice the activation effect compared to including potassium chloride in the buffer solution before freeze-drying [1]. When freezing at −20 °C instead of in liquid nitrogen, even better activation was observed with fumed silica. We hypothesize that the activation of SC in hexane by immobilization of the enzyme on fumed silica is likely due to the distribution of the enzyme on the large surface area of fumed silica. This alleviates mass transfer limitations.     

A silicon budget for an Alaskan arctic lake

The cycling of dissolved reactive silicate (DRS) and sedimentary biogenic SiO₂ has been examined in ultraoligotrophic Toolik Lake, Alaska. Watershed output of DRS (∼ 7 mmol m ^{− 2} yr ⁻¹) is similar to other arctic study sites, but a short water residence time results in the poor retention of DRS (∼17%) within the lake. Biogenic SiO₂ concentrations in surficial sediments average 123 mg g⁻¹ with the highest concentrations arising from the production of benthic diatoms in the littoral zone. Lake water DRS concentrations are highest prior to spring flow and photic zone concentrations exceed 23 μmol 1⁻¹ at the time of greatest primary production. Wintertime increases in watercolumn DRS concentrations and spring and summer pore water DRS flux estimates indicate that internal cycling within the lake may supply an amount of DRS equivalent to that which biologically utilized.     

以短肽组装体为模板仿生矿化二氧化硅纳米管

目的 二氧化硅纳米管由于具有生物相容性好、光学性质优异等特殊性能在不同领域展现出良好的应用前景，其尺寸和形貌可显著影响材料性质。为制备尺寸较大的纳米管并拓展其在不同领域的应用，本研究选择尺寸较大的多肽组装体为模板，进行二氧化硅的仿生矿化。方法 以Bola型多肽Ac-KI₃VK-CONH₂自组装形成的尺寸较大（直径约40 nm）的纳米管为模板，通过仿生矿化的方法制备二氧化硅纳米材料。首先考察了多肽纳米管的稳定性，发现在稀释、加入有机溶剂和改变溶液pH值时，纳米管的形貌均被破坏，展示出较差的稳定性。在此基础上，以该多肽纳米管为模板，选择反应速率较快的正硅酸甲酯（TMOS）为前驱体仿生矿化二氧化硅纳米材料，探索了不同矿化条件对二氧化硅纳米管尺寸和形貌的影响。结果 以反应速率较快的TMOS为硅源、体积百分比浓度为1.11%~3.33%、溶液为中性或者弱碱性时能够矿化形成形貌和尺寸较大且分布均匀的二氧化硅纳米管。结论 通过选择合适的多肽组装体模板和反应速率快的TMOS为硅源，成功制备出了尺寸较大的二氧化硅纳米管，这为拓展其在不同领域的应用奠定了基础，具有重要意义。     

Revisiting the Role of Conductivity and Polarity of Host Materials for Long‐Life Lithium–Sulfur Battery

Despite their high theoretical energy density and low cost, lithium–sulfur batteries (LSBs) suffer from poor cycle life and low energy efficiency owing to the polysulfides shuttle and the electronic insulating nature of sulfur. Conductivity and polarity are two critical parameters for the search of optimal sulfur host materials. However, their role in immobilizing polysulfides and enhancing redox kinetics for long‐life LSBs are not fully understood. This work has conducted an evaluation on the role of polarity over conductivity by using a polar but nonconductive platelet ordered mesoporous silica (pOMS) and its replica platelet ordered mesoporous carbon (pOMC), which is conductive but nonpolar. It is found that the polar pOMS/S cathode with a sulfur mass fraction of 80 wt% demonstrates outstanding long‐term cycle stability for 2000 cycles even at a high current density of 2C. Furthermore, the pOMS/S cathode with a high sulfur loading of 6.5 mg cm^?2 illustrates high areal and volumetric capacities with high capacity retention. Complementary physical and electrochemical probes clearly show that surface polarity and structure are more dominant factors for sulfur utilization efficiency and long‐life, while the conductivity can be compensated by the conductive agent involved as a required electrode material during electrode preparation. The present findings shed new light on the design principles of sulfur hosts towards long‐life and highly efficient LSBs.     

Immobilization rapidly selects for chemoresistant ovarian cancer cells with enhanced ability to enter dormancy

Around 20–30% of ovarian cancer patients exhibit chemoresistance, but there are currently no methods to predict whether a patient will respond to chemotherapy. Here, we discovered that chemoresistant ovarian cancer cells exhibit enhanced survival in a quiescent state upon experiencing the stress of physical confinement. When immobilized in stiff silica gels, most ovarian cancer cells die within days, but surviving cells exhibit hallmarks of single-cell dormancy. Upon extraction from gels, the cells resume proliferation but demonstrate enhanced viability upon reimmobilization, indicating that initial immobilization selects for cells with a higher propensity to enter dormancy. RNA-seq analysis of the extracted cells shows they have signaling responses similar to cells surviving cisplatin treatment, and in comparison to chemoresistant patient cohorts, they share differentially expressed genes that are associated with platinum-resistance pathways. Furthermore, these extracted cells demonstrate greater resistance to cisplatin and paclitaxel, despite being proliferative. In contrast, serum starvation and hypoxia could not effectively select for chemoresistant cells upon removal of the environmental stress. These findings demonstrate that ovarian cancer chemoresistance and the ability to enter dormancy are linked, and immobilization rapidly distinguishes chemoresistant cells. This platform could be suitable for mechanistic studies, drug development, or as a clinical diagnostic tool.     

MICROMORPHOGENESIS DURING DIATOM WALL FORMATION PRODUCES SILICEOUS NANOSTRUCTURES WITH DIFFERENT PROPERTIES1

Micromorphogenesis within the silica deposition vesicle (SDV) of the diatom Pinnularia viridis (Nitzsh) Ehrenb. resulted in distinct silica nanostructures and layers within forming valves and girdle bands. These siliceous components were similarly disclosed following alkaline etching of mature valves/girdle bands, where their different susceptibilities to dissolution over time resulted from apparent differences in silica density and/or chemistry. The bulk of silica appeared to be deposited at the interface of the forming valve or girdle band with the silicalemma and occurred by the outward expansion of microfibrils of silica that aligned perpendicularly to the silicalemma. Microfibrils originated from both sides of the “silica lamella,” the first nanostructure formed within the SDV, and several silica species of distinct nanostructure and density resulted, including distinctive inner and outermost silica “coverings” of mature valves/girdle bands and the central and terminal nodules. Not all silica deposition and micromorphogenesis occurred in contact with the expanding silicalemma, but was somehow directed within the SDV cavity, and resulted in the distinct silica layers that lined the raphe fissures and poroids. Following alkaline etching, the inner surfaces of valves/girdle bands, as well as the silica layers lining the raphes, poroids, and slits, were determined to be significantly more resistant to alkaline etching than the exterior surfaces, while the outer silica coating and the nodules were quickly dissolved. The processes of micromorphogenesis must have exerted precise control over the chemical nature of the silica formed at different positions within the SDV and affected the overall structure and function of the diatom wall.     

Amperometric biosensor based on enzymes immobilized in hybrid mesoporous membranes for the determination of acetylcholine

Acetylcholine sensor is successfully prepared by using immobilized enzymes, i.e., acetylcholinesterase and choline oxidase within separate hybrid mesoporous silica membranes with 12 nm pore diameter (F127M). The measurement was based on the detection of hydrogen peroxide produced by two sequential enzyme reactions. The determination range and the response time are 6.0–800 μM and within approximately 3 min, respectively. The sensor is very stable compared to free enzymes and 80% of the initial response was maintained even after storage for 80 days. These results show that two enzymes are successfully immobilized and well stabilized, and at the same time, two sequential enzyme reactions efficiently proceed within the separate hybrid mesoporous membranes. Further, we studied the possible detection of organophosphorus pesticides in terms of the inhibition of acetylcholinesterase activity, i.e., the decrease of current response, and demonstrated that the nanomolar concentrations of pesticide (DZN-oxon) can be detected with our sensor.     

羧基化介孔二氧化硅纳米颗粒递送PD-L1抑制剂治疗膀胱癌的作用研究

摘要 目的：构建羧基化介孔二氧化硅纳米颗粒（COOH-MSN）递送PD-L1抑制剂治疗膀胱癌。方法：构建负载PD-L1抑制剂的COOH-MSNs，透射电镜检测纳米颗粒的特征，zeta电位分析仪检测纳米颗粒的电位变化；流式细胞术检测血液中T细胞和CD8⁺T细胞的比例；MTT实验检测细胞增殖；构建小鼠荷瘤模型，HE染色检测基本的病理学变化，免疫组化检测ki-67的表达。结果：透射电镜结果显示纳米颗粒呈圆形，直径约为100 nm；COOH-MSNs表面带负电荷，BSA呈强负电性，BSA包封后纳米材料整体负电荷增强；纳米材料可显著提高T细胞和CD8⁺T细胞的比例，并进一步抑制膀胱癌细胞的增殖；动物实验结果显示纳米材料可抑制移植瘤的生长，且移植瘤内淋巴细胞的数量显著升高；免疫组化结果显示相对于PD-L1抑制剂组，纳米材料组ki-67增殖指数显著减低；HE染色结果显示PD-L1抑制剂组肾组织内可观察到血管充血、扩张和较多炎细胞浸润，而纳米材料组肾组织损伤程度显著降低。结论：我们构建了一种负载有PD-L1抑制剂的COOH-MSNs，可有效激活抗肿瘤免疫反应，并降低对正常器官的损伤。     

The effect of binding of spider-derived antimicrobial peptides, oxyopinins, on lipid membranes

Oxyopinins (Oxki1 and Oxki2) are antimicrobial peptides isolated from the crude venom of the wolf spider Oxyopes kitabensis. The effect of oxyopinins on lipid bilayers was investigated using high-sensitivity titration calorimetry and ³¹P solid-state NMR spectroscopy. High-sensitivity titration calorimetry experiments showed that the binding of oxyopinins was exothermic, and the binding enthalpies (ΔH) to 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine (POPC) small unilamellar vesicles (SUVs) were − 18.1 kcal/mol and − 15.0 kcal/mol for Oxki1 and Oxki2, respectively, and peptide partition coefficient (K_p) was found to be 3.9 × 10³ M^− 1. ³¹P NMR spectra of 1,2-dielaidoyl-sn-glycero-3-phosphoethanolamine (DEPE) membranes in the presence of oxyopinins indicated that they induced a positive curvature in lipid bilayers. The induced positive curvature was stronger in the presence of Oxki2 than in the presence of Oxki1. ³¹P NMR spectra of phosphaditylcholine (PC) membranes in the presence of Oxki2 showed that Oxki2 produced micellization of membranes at low peptide concentrations, but unsaturated PC membranes or acidic phospholipids prevented micellization from occurring. Furthermore, ³¹P NMR spectra using membrane lipids from E. coli suggested that Oxki1 was more disruptive to bacterial membranes than Oxki2. These results strongly correlate to the known biological activity of the oxyopinins.