Effect of salvianolic acid B-loaded mesoporous silica nanoparticles on myocardial ischemia-reperfusion injury

Background:Currently,no drugs can specifically improve clinical cardiac ischemia-reperfusion injury or the prognosis of hemodialysis.Salvianolic acid B(SalB)is a widely used cardiac protectant;however,its clinical application is limited by its low oral bioavailability and poor intestinal absorption.The exploration of its preparation and clinical applications has become a research hotspot in recent years.Methods:To determine whether mesoporous silica nanoparticles(MSNs)efficiently delivered SalB to the heart and SalB@MSNs-RhB reduced myocardial ischemia-reperfusion injury,we constructed a myocardial ischemia-reperfusion male rat model,hypoxia/reoxygenation cardiomyocytes,and treated them with SalB@MSNs-RhB.Results:SalB@MSNs-RhB showed improved bioavailability,therapeutic effect,heightened JAK2/STAT3-dependent pro-survival signaling,and antioxidant responses,thereby protecting cardiomyocytes from ischemia-reperfusion injury-induced oxidative stress and apoptosis.Conclusion:This use of SalB-loaded nanoparticles and investigation of their mechanism of action may provide a new strategy for treating cardiomyocytes.Thus,hypoxia/reoxygenation promotes the clinical application of SalB.

DMSNs对酚类化合物的吸附及降解研究进展

酚类化合物广泛存在于空气、废水和土壤中,严重危害自然环境和人类健康。加强此类化合物的处理是科研工作者的研究重点。本文总结了树枝状介孔SiO_(2)纳米粒子(dendritic mesoporous silica nanoparticles,DMSNs)对酚类化合物吸附、降解的最新研究进展。重点探讨了DMSNs催化剂的设计思路以及在对硝基苯酚、苯酚、双酚A、邻氯苯酚等多种酚类化合物方面的应用和反应机制,为后续设计出绿色环保、吸附降解性能优异的功能材料提供了理论基础,并且展望了此类催化剂降解酚类污染物的发展方向。

Synthesis and Characterization of Carboxyl-terminated Polyethylene Glycol Functionalized Mesoporous Silica Nanoparticles

Colloidal mesoporous silica nanoparticles functionalized with carboxy-terminated polyethylene glycol(CMS-PEG-COOH) were successfully synthesized by covalently grafting dicarboxy-terminated polyethylene glycol(HOOC-PEG-COOH) on the surface of the amino functionalized CMS nanoparticles with amide bond as a cross linker. Moreover, the structural and particle properties of CMS-PEG-COOH were characterized by nuclear magnetic resonance spectroscopy(1 H-NMR), transmission electron microscopy(TEM), dynamic light scattering(DLS), nitrogen adsorption-desorption measurements, X-ray diffraction(XRD), and Fourier transform infrared spectroscopy(FT-IR). The nanomaterials presented a relatively uniform spherical shape morphology with diameters of about 120 nm,and favorable dispersibility in weak acid solution. The CMSPEG-COOH exhibited no changes in the state of amorphous, while the mesopores sizes of 5.25 nm might provide the nanomaterials with large capacity for the loading and releasing of drugs. So the results indicated that CMSPEG-COOH might be a critical nanomaterial for drug delivery system in the future.

刺激响应型MSNs负载蒽醌修饰物4S对三阴性乳腺癌的体外研究

目的:探讨刺激响应型介孔二氧化硅纳米粒(MSNs-SS-HA)作为药物递送系统是否能提高蒽醌修饰物4S对三阴性乳腺癌(TNBC)细胞的靶向性、生物利用度,并降低对正常细胞的毒性。方法:后修饰法制备功能化的纳米粒MSNs-SS-HA,利用透射电镜、马尔文粒径仪、傅里叶红外光谱和元素分析等对纳米粒进行表征。体外透析实验检测MSNs@4S和MSNs-SSHA@4S在不同浓度的谷胱甘肽缓冲溶液中的释放行为。MTT试验测定游离4S和载药纳米粒对TNBC细胞MDA-MB231、乳腺癌细胞MCF-7和乳腺正常细胞MCF-10A的抑制活性。激光共聚焦显微镜观察蒽醌修饰物4S和载药纳米粒在不同细胞中的摄取情况。结果:成功制备功能化的载药纳米粒MSNs-SS-HA@4S,其载药量和包封率分别为(17.43±1.2)%和(90.56±1.1)%。载药纳米粒MSNs-SS-HA@4S具有还原响应特性,同时具有缓控释药作用。在相同浓度下,MSNs-SS-HA@4S对MDA-MB231细胞的毒性高于MCF-10A细胞,而对MCF-7细胞的抗肿瘤活性较弱(P<0.05)。体外细胞摄取实验表明,MSNs-SS-HA@4S能够靶向CD44受体高表达的TNBC细胞MDA-MB231,可能通过CD44受体介导的内吞作用进入细胞,揭示了MSNs-SS-HA@4S具有肿瘤靶向治疗潜能。结论:MSNs-SS-HA@4S提高了蒽醌修饰物4S增效减毒的功效,为TNBC的靶向治疗提供新思路。

DMSNs基功能材料对染料吸附降解性能的研究进展

染料作为工业废水污染物对人类健康和生态环境造成了严重危害,如何绿色高效的去除废水中染料及其衍生物具有重要意义。树枝状介孔二氧化硅纳米粒子(DMSNs)具有中心辐射状孔道、比表面积大、孔隙率高等特点,因而在染料治理领域备受青睐。本文介绍了DMSNs对染料吸附降解性能的最新研究进展,涉及染料主要包括亚甲基蓝、甲基橙、刚果红、孔雀石绿等。重点阐述了DMSNs基吸附剂的制备方法及其对染料的吸附降解效率,为后续相关研究提供参考。最后对DMSNs基功能材料处理染料的发展趋势进行了总结与展望。

pH-responsive mesoporous silica nanoparticles employed in controlled drug delivery systems for cancer treatment

In the fight against cancer, controlled drug delivery systems have emerged to enhance the therapeutic efficacy and safety of anti-cancer drugs. Among these systems, mesoporous silica nanoparticles(MSNs) with a functional surface possess obvious advantages and were thus rapidly developed for cancer treatment. Many stimuli-responsive materials, such as nanoparticles, polymers, and inorganic materials, have been applied as caps and gatekeepers to control drug release from MSNs. This review presents an overview of the recent progress in the production of pH-responsive MSNs based on the pH gradient between normal tissues and the tumor microenvironment. Four main categories of gatekeepers can respond to acidic conditions. These categories will be described in detail.

Preparation and Characterization of Carboxyl Functionalized Fluorescent Mesoporous Silica Nanoparticles Containing 8-Hydroxyquinolinate Zinc Complexes

Fluorescent mesoporous silica nanoparticles functionalized with carboxyl group(Znq-CMSCOOH) were successfully synthesized by in situ formation route of 8-hydroxyquinolinate zinc complexes in channels of mesoporous silica nanoparticles and post-grafting of carboxyl group on the surface. Moreover,the particle size and structural properties of Znq-CMS-COOH were characterized by transmission electron microscopy(TEM),field emission scanning electron microscopy(FE-SEM),dynamic light scattering(DLS),Fourier transform infrared spectroscopy(FT-IR),UV-vis spectrometer, fluorescence spectrometer and nitrogen adsorption-desorption measurements. The obtained results suggest that the Znq-CMS-COOH presents the uniform spherical shape with the mean diameter of about 85 nm and the obvious wormhole arrangement mesoporous. In addition, the Znq-CMS-COOH possesses green fluorescence with the emission peaks at 495 nm. So the Znq-CMS-COOH, which is beneficial to further modification and tracing, might be a great potential carrier for applying in drug delivery system in the future.

Characterization of modified mesoporous silica nanoparticles as vectors for siRNA delivery

Gene therapy using siRNA molecules is nowadays considered as a promising approach. For successful therapy, development of a stable and reliable vector for siRNA is crucial. Non-viral and non-organic vectors like mesoporous silica nanoparticles(MSN) are associated with lack of most viral vector drawbacks, such as toxicity, immunogenicity, but also generally a low nucleic acid carrying capacity. To overcome this hurdle, we here modified the pore walls of MSNs with surface-hyperbranching polymerized poly(ethyleneimine)(hbPEI), which provides an abundance of amino-groups for loading of a larger amount of siRNA molecules via electrostatic adsorption. After loading, the particles were covered with a second layer of pre-polymerized PEI to provide better protection of siRNA inside the pores, more effective cellular uptake and endosomal escape. To test the transfection efficiency of PEI covered si RNA/MSNs, MDA-MB 231 breast cancer cells stably expressing GFP were used. We demonstrate that PEI-coated si RNA/MSN complexes provide more effective delivery of si RNAs compared to unmodified MSNs. Thus, it can be concluded that appropriately surface-modified MSNs can be considered as prospective vectors for therapeutic siRNA delivery.

Synthesis of Mesoporous Silica Nanoparticles with Tunable Shape and Size

The structural and morphological properties of mesoporous silica nanoparticles( MSNs) have dramatical influence on their in vivo biological behaviors,and thereby synthesis of MSNs with well-defined shape and size has recently attracted much more attention in the biomedical field. The synthesis of MSNs with controllable size and shape was presented by controlling the reaction temperature and the concentration of templating agent(cetyltrimethylammonium bromide,CTAB). The results indicated that MSNs were larger in particle size and more round in shape with increasing of the reaction temperature,but their particle size and dispersivity became smaller and poorer as CTAB concentration increased. Therefore,the particle size and shape of MSNs can be tuned by using the optimal synthesis conditions for specific biomedical applications.

Incorporation of Sphingosine 1-Phosphate Loaded Mesoporous Silica Nanoparticles into Poly ( L-lactic acid ) Nanofibrous Scaffolds for Bone Tissue Engineering

Controlled release of the functional factors is the key to improve clinical therapeutic efficacy during the tissue repair and regeneration.The three-dimensional(3D)scaffold can provide not only physical properties such as high strength and porosity but also an optimal environment to enhance tissue regeneration.Sphingosine1-phosphate(S1P),an angiogenic factor,was loaded into mesoporous silica nanoparticles(MSNs)and then incorporated into poly(L-lactic acid)(PLLA)nanofibrous scaffold,which was fabricated by thermally induced phase separation(TIPS)method.The prepared scaffolds were examined by attenuated total reflection Fourier transform infrared spectroscopy(ATR-FTIR),scanning electron microscopy(SEM),and transmission electron microscopy(TEM)and compressive mechanical test.The ATR-FTIR result demonstrated the existence of MSNs in the PLLA nanofibrous scaffold.The SEM images showed that PLLA scaffold had regular pore channel,interconnected pores and nanofibrous structure.The addition of MSNs at appropriate content had no visible effect on the structure of scaffold.The compressive modulus of scaffold containing MSNs was higher than that of the scaffold without MSNs.Furthermore,fluorescein isothiocyanate(FITC)was used as model molecule to investigate the release behavior of S1P from MSNsincorporated PLLA(MSNs/PLLA)nanofibrous scaffold.The result showed that the composite scaffold largely reduced the initial burst release and exhibited prolonged release of FITC than MSNs.Thus,these results indicated that S1P-loaded composite nanofibrous scaffold has potential applications for bone tissue engineering.

Development of phosphonate-terminated magnetic mesoporous silica nanoparticles for pH-controlled release of doxorubicin and improved tumor accumulation

In this study,phosphonate-terminated magnetic mesoporous nanoparticles(pMMSNs)was designed by incorporation of MNPs in the center of mesoporous silica nanoparticles(MSNs)and followed by grafting phosphonate group on to the surface of MMSNs.The carrier exhibited a typical superparamagnetic feature and the saturation magnetization was 4.89 emu/g measured by vibrating sample magnetometer(VSM).pMMSNs had a spherical morphology and a pore size of 2.2 nm.FromN2 adsorption-desorption analysis,pMMSNs had a surface area of 613.4 m^(2)/g and a pore volume of 0.78 cm^(3)/g.Phosphonate modification improved the colloidal stability of MMSNs,and the hydrodynamic diameter of pMMSNs was around 175 nm.The hydrophilic phosphonate group significantly enhanced the negative surface charge of MMSNs from -19.3 mV to -28.8 mV pMMSNs with more negative surface charge had a 2.3-fold higher drug loading capacity than that of MMSNs.In addition,the rate and amount of release of doxorubicin(DOX)from DOX/pMMSNs was pH-dependent and increased with the decrease of pH.At pH 7.4,the release amount was quite low and only approximately 17wt%ofDOXwasreleasedin48h.AtpH5.0and3.0,the release rate increased significantly and the release amount achieved 31 wt%and 60 wt%in 48 h,respectively.To evaluate the magnetic targeting performance ofpMMSNs,FITC labeledpMMSNswas injected into mice bearing S180 solid tumor.FITC labeledpMMSNscontrolled by an external magnetic field showed higher tumor accumulation and lower normal tissue distribution.

Dual responsive block copolymer coated hollow mesoporous silica nanoparticles for glucose-mediated transcutaneous drug delivery

A self-regulated anti-diabetic drug release device mimicking pancreatic cells is highly desirable for the therapy of diabetes. Herein, a glucose-mediated dual-responsive drug delivery system, which combines pH-and H_(2)O_(2)-responsive block copolymer grafted hollow mesoporous silica nanoparticles(HMSNs)with microneedle(MN) array patch, has been developed to achieve self-regulated administration.The poly[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl acrylate]-b-poly[2-(dimethylamino)ethyl methacrylate](PPBEM-b-PDM) polymer serves as gate keeper to prevent drug release from the cavity of HMSNs at normoglycemic level. In contrast, the drug release rate is significantly enhanced upon H_(2)O_(2)and pH stimuli due to the chemical change of H_(2)O_(2)sensitive PPBEM block and acid responsive PDM block. Therefore, incorporation of anti-diabetic drug and glucose oxidase(GOx, which can oxidize glucose to gluconic acid and in-situ produce H_(2)O_(2)) into stimulus polymer coated HMSNs results in a glucose-mediated MN device after depositing the drug-loaded nanoparticles into MN array patch. Both in vitro and in vivo results show this MN device presents a glucose mediated self-regulated drug release characteristic, which possesses a rapid drug release at hyperglycemic level but retarded drug release at normoglycemic level. The result indicates that the fabricated smart drug delivery system is a good candidate for the therapy of diabetes.

Synthesis of Novel Virus-Like Mesoporous Silica-ZnO-Ag Nanoparticles and Quercetin Synergize with NIR Laser for Omicron Mutated Covid-19 Virus Infectious Diseases Treatment

This work shows that novel virus-like mesopore silica-zinc oxide/Ag nanoparticles (SZnOAg) synthesized and professionally collected on NIR laser irradiation with quercetin to improve the elimination the mutated virus as a biomedical application. A unique type of silica nanoparticles with a self-in- flating tubular surface has been successfully synthesized using a novel single-micelle epitaxial growth process. The properties of the nanoparticles can be tuned with respect to their core diameter, tubular length, and outer diameter. Due to their biomimetic appearance, they can rapidly transform living cells into virus-like particles, this SZnOAg nanomaterial has specific elimination effect on bacteriophage and Covid-19. Using epitaxial growth, we can construct virus-like structures that can be used for biomedicine applications. These nanomaterials and NIR laser could open the way to a new range of antiviral materials, due to the low-efficiency cellular uptake of current nanoparticles, their applications in the biomedical field are limited. Herein, it clearly shows that novel mesoporous silica nanoparticles can be easily exhibited superior cellular uptake property.

Coercivity Ageing Effect on FePt Nanoparticles in Mesoporous Silica via Stepwise Synthesis Strategy

FePt nanoparticles in mesoporous silica are fabricated by a simple stepwise synthesis strategy.A pre-annealing temperature-dependent coercivity-ageing effect in FePt nanoparticles is observed at room temperature.For facecentered cubic（fcc）structured FePt nanoparticles,the ageing effect is sensitive to the pre-annealing temperature,especially when the temperature is close to the phase-transition.The special magnetic behavior of FePt nanoparticles reveals that the physical properties gradually change between fee and face-centered tetragonal structures,and will deepen our understanding of the mechanism of such magnetism in FePt nanoparticles.

Preparation,Characterization and Catalytic Activity of Palladium Nanoparticles Embedded in the Mesoporous Silica Matrices

Novel in-situ reduction approach was applied for the synthesis of palladium nanoparticles in the pores of mesoporous silica materials with grafted siliconhydride groups. Matrices possessing different structural properties (MCM-41, SBA-15 and Silochrom) were used. Samples were studied by nitrogen adsorption-desorption method, low-angle X-ray diffraction, transmission electron microscopy (TEM) and FT-IR/PAS spectroscopy. The temperature-programmed oxidation (TPO) and reduction (TPR) methods were applied to examine reducibility of palladium species. Palladium containing catalysts were tested in methane oxidation reaction. It was demonstrated that relatively large pores in SBA-15 type silica facilitated formation of well-dispersed palladium nanoparticles confined in the pores channels. In the case of MCM-41 support, metallic palladium nanoparticles were formed on the external surface. The obtained materials showed high catalytic activity. Lower activity of the samples containing small crystallites located in the pore volume at high temperatures was related to worse accessibility of active sites to the reation mixture.

Amphipathicity mediated endocytosis of mesoporous silica nanoparticles with tunable frameworks

Due to the amphiphilic nature of phospholipids in the cell membrane,the amphipathicity of the nanomedicine plays a crucial role in the endocytosis.However,limited biological characterization methods restrict the study of the state of nanoparticles with different amphiphilicities on cell membranes.The understanding of interaction of amphiphilic particle with cell membrane is still lacking.Herein,by combining the dissipative particle dynamics(DPD)with the framework construction of mesoporous silica nanoparticles(MSNs),we demonstrate the enhanced endocytosis induced by the hydrophobicity.DPD results confirm that the presence of hydrophobic groups on the surface of nanoparticles can disturb the integrity of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine(POPC)membrane and induce activation of phospholipids to a higher energy level,thereby facilitating the wrapping of nanoparticles.To validate the simulation findings,uniform MSNs with hydrophilic pure silica framework and two types of amphiphilic MSNs with varying hydrophilic organic groups in the framework are rationally synthesized by using different silane precursors.The obtained three kinds of MSNs show similar diameter(~100 nm)and mesopores(~2 nm),but distinct hydrophobicity/hydrophilicity ratio.The phenyl-bridged MSN with a carbon content of 27.1%exhibits enhanced cellular uptake,consistent with the theoretical simulation results.This work sheds light on how the surface amphipathicity influences endocytosis through the interaction with cell membrane.

Dendritic mesoporous silica nanoparticles for enzyme immobilization

Dendritic mesoporous silica nanoparticles(DMSNs)are a new class of solid porous materials used for enzyme immobilization support due to their intrinsic characteristics,including their unique open central-radial structures with large pore channels and their excellent biocompatibility.In this review,we review the recent progress in research on enzyme immobilization using DMSNs with different structures,namely,flower-like DMSNs and tree-branch-like DMSNs.Three DMSN synthesis methods are briefly compared,and the distinct characteristics of the two DMSN types and their effects on the catalytic performance of immobilized enzymes are comprehensively discussed.Possible directions for future research on enzyme immobilization using DMSNs are also proposed.

In Situ Synthesis of Fluorescent Mesoporous Silica–Carbon Dot Nanohybrids Featuring Folate Receptor-Overexpressing Cancer Cell Targeting and Drug Delivery

Multifunctional nanocarrier-based theranostics is supposed to overcome some key problems in cancer treatment.In this work,a novel method for the preparation of a fluorescent mesoporous silica–carbon dot nanohybrid was developed.Carbon dots(CDs),from folic acid as the raw material,were prepared in situ and anchored on the surface of amino-modified mesoporous silica nanoparticles(MSNs–NH2) via a microwave-assisted solvothermal reaction.The as-prepared nanohybrid(designated MSNs–CDs) not only exhibited strong and stable yellow emission but also preserved the unique features of MSNs(e.g.,mesoporous structure,large specific surface area,and good biocompatibility),demonstrating a potential capability for fluorescence imagingguided drug delivery.More interestingly,the MSNs–CDs nanohybrid was able to selectively target folate receptor-overexpressing cancer cells(e.g.,HeLa),indicating that folic acid still retained its function even after undergoing the solvothermal reaction.Benefited by these excellent properties,the fluorescent MSNs–CDs nanohybrid can be employed as a fluorescence-guided nanocarrier for the targeted deliveryof anticancer drugs(e.g.,doxorubicin),thereby enhancing chemotherapeutic efficacy and reducing side effects.Our studies may provide a facile strategy for the fabrication of multifunctional MSN-based theranostic platforms,which is beneficial in the diagnosis and therapy of cancers in future.

Mesoporous SiO_2 Nanoparticles:A Unique Platform Enabling Sensitive Detection of Rare Earth Ions with Smartphone Camera

Fast and sensitive detection of dilute rare earth species still represents a challenge for an on-site survey of new resources and evaluation of the economic value. In this work, a robust and low-cost protocol has been developed to analyze the concentration of rare earth ions using a smartphone camera. The success of this protocol relies on mesoporous silica nanoparticles(MSNs) with large-area negatively charged surfaces, on which the rare earth cations(e.g., Eu^(3+)) are efficiently adsorbed through electrostatic attraction to enable a ‘‘concentrating effect''. The initial adsorption rate is as fast as 4025 mg(g min)^(-1), and the adsorption capacity of Eu^(3+)ions in the MSNs is as high as 4730 mg g^(-1)(equivalent to ～41.2 M) at 70 °C. The concentrated Eu^(3+)ions in the MSNs can form a complex with a light sensitizer of 1,10-phenanthroline to significantly enhance the characteristic red emission of Eu^(3+)ions due to an ‘‘antenna effect'' that relies on the efficient energy transfer from the light sensitizer to the Eu^(3+)ions.The positive synergy of ‘‘concentrating effect'' and ‘‘antenna effect'' in the MSNs enables the analysis of rare earth ions in a wide dynamic range and with a detection limit down to ～80 nM even using a smartphone camera. Our results highlight the promise of the protocol in fieldwork for exploring valuable rare earth resources.

Controlling the Shape, Pore Size and Surface Area of Prepared Mesoporous Silica Particles by Altering the Molar Concentration of Tetramethoxysilane

In recent days, the applications of silica-based nanoparticles have gained much attention. The preparation of mesoporous silicas is usually achieved via the modified Stöber method, the reaction attained by the hydrolysis and condensation of silica precursors present within a medium containing template, solvent, deionized water (DI-W) and base. Therefore, the current study aimed to prepare and characterize mesoporous silicas by using tetramethoxysilane (TMOS) as silica precursor and ethylene glycol (Et-G) as solvent. The study was based on the template dodecyltrimethylammonium bromide (C12TMABr) and sodium hydroxide used as an alkaline agent. Mesoporous silicas were prepared in various batches based on TMOS molar concentration, ionized water, NaOH, and other solvents. The characterization of mesoporous silicas was achieved based on their specific surface area, pore size distribution and morphology using different instruments: Brunauer, Emmett & Teller (BET), scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FT-IR), and thermalgravimetric analysis (TGA). The study revealed that shape, average particle sizes “35 to 550 nm”, average pore radius “1.62 - 4.5 nm” and surface area “350 - 1204 m2·g-1” of obtained mesoporous silica particles were altered based on precursor concentration and other factors. Therefore, it is important to get the most suitable concentration of all chemicals in the preparation of mesoporous silicas to control the particle characteristics to use them upon their further applications. This is the baseline study that provides details regarding prepared silica particles with controlled characteristics, and more studies related to its applications are still in process.