Pores Of Mesoporous Silica Nanoparticles Research Articles

Enhanced Efficacy against Drug-Resistant Tumors Enabled by Redox-Responsive Mesoporous-Silica-Nanoparticle-Supported Lipid Bilayers as Targeted Delivery Vehicles.

Multidrug resistance (MDR) is frequently induced after long-term exposure to reduce the therapeutic effect of chemotherapeutic drugs, which is always associated with the overexpression of efflux proteins, such as P-glycoprotein (P-gp). Nano-delivery technology can be used as an efficient strategy to overcome tumor MDR. In this study, mesoporous silica nanoparticles (MSNs) were synthesized and linked with a disulfide bond and then coated with lipid bilayers. The functionalized shell/core delivery systems (HT-LMSNs-SS@DOX) were developed by loading drugs inside the pores of MSNs and conjugating with D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) and hyaluronic acid (HA) on the outer lipid surface. HT-LMSNs-SS and other carriers were characterized and assessed in terms of various characteristics. HT-LMSNs-SS@DOX exhibited a dual pH/reduction responsive drug release. The results also showed that modified LMSNs had good dispersity, biocompatibility, and drug-loading capacity. In vitro experiment results demonstrated that HT-LMSNs-SS were internalized by cells and mainly by clathrin-mediated endocytosis, with higher uptake efficiency than other carriers. Furthermore, HT-LMSNs-SS@DOX could effectively inhibit the expression of P-gp, increase the apoptosis ratios of MCF-7/ADR cells, and arrest cell cycle at the G0/G1 phase, with enhanced ability to induce excessive reactive oxygen species (ROS) production in cells. In tumor-bearing model mice, HT-LMSNs-SS@DOX similarly exhibited the highest inhibition activity against tumor growth, with good biosafety, among all of the treatment groups. Therefore, the nano-delivery systems developed herein achieve enhanced efficacy towards resistant tumors through targeted delivery and redox-responsive drug release, with broad application prospects.

Conformation-Switchable Polypeptides as Molecular Gates for Controllable Drug Release.

The control over secondary structure has been widely studied to regulate the properties of polypeptide materials, which is used to change their functions in situ for various biomedical applications. Herein, we designed and constructed enzyme-responsive polypeptides as gating materials for mesoporous silica nanoparticles (MSNs), which underwent a distorted structure-to-helix transition to promote the release of encapsulated drugs. The polypeptide conjugated on the MSN surface adopted a negatively charged, distorted, flexible conformation, covering the pores of MSN to prevent drug leakage. Upon triggering by alkaline phosphatase (ALP) overproduced by tumor cells, the polypeptide transformed into positively charged, α-helical, rigid conformation with potent membrane-penetrating capabilities, which protruded from the MSN surface to uncover the pores. Such a transition thus enabled cancer-selective drug release and cellular internalization to efficiently kill tumor cells. This study highlights the important role of chain flexibility in modulating the biological function of polypeptides and provides a new application paradigm for synthetic polypeptides with secondary-structure transition.

A Biodegradable Nano-Drug Delivery Platform for Co-Delivery of Minocycline and Chitosan to Achieve Efficient and Safe Non-Surgical Periodontitis Therapy.

Mesoporous silica nanoparticles (MSN) are widely used as ideal nanovehicles for the delivery of chemotherapeutic drugs. However, the balance between high anti-periodontitis activity and low biotoxicity has been challenging to maintain in most relevant studies owing to the slow degradation of silica in living organisms. In this study, -responsive hydroxyapatite (HAP) was doped into the MSN skeleton, and the chemotherapeutic drug minocycline hydrochloride (MH) was loaded into the pores of MSN, forming a negatively charged drug delivery system. Cationic chitosan (COS) is a biodegradable material with high antibacterial performance and good biosafety. In this study, COS was immobilized on the surface of the drug-loaded particles through stable charge interaction to construct a composite drug delivery system (MH@MSNion@COS). In vitro and cellular experiments demonstrated effective degradation of the nanocarrier system and synchronized controlled release of the drug. Notably, compared with single MH administration, this system, in which MH and COS jointly regulated the expression levels of periodontitis- associated inflammatory factors (TNF-α, IL-6, IL-1β, and iNOS), better inhibited the progress of periodontitis and induced tissue regeneration without showing significant toxic side effects in cells. This system provides a promising strategy for the design of intelligent, efficient, and safe anti-periodontitis drug delivery systems.

Patterned immobilization of polyoxometalate-loaded mesoporous silica particles via amine-ene Michael additions on alkene functionalized surfaces

Polyoxometalates (POM) are anionic oxoclusters of early transition metals that are of great interest for a variety of applications, including the development of sensors and catalysts. A crucial step in the use of POM in functional materials is the production of composites that can be further processed into complex materials, e.g. by printing on different substrates. In this work, we present an immobilization approach for POMs that involves two key processes: first, the stable encapsulation of POMs in the pores of mesoporous silica nanoparticles (MSPs) and, second, the formation of microstructured arrays with these POM-loaded nanoparticles. Specifically, we have developed a strategy that leads to water-stable, POM-loaded mesoporous silica that can be covalently linked to alkene-bearing surfaces by amine-Michael addition and patterned into microarrays by scanning probe lithography (SPL). The immobilization strategy presented facilitates the printing of hybrid POM-loaded nanomaterials onto different surfaces and provides a versatile method for the fabrication of POM-based composites. Importantly, POM-loaded MSPs are useful in applications such as microfluidic systems and sensors that require frequent washing. Overall, this method is a promising way to produce surface-printed POM arrays that can be used for a wide range of applications.

Confined growth of Ag nanogap shells emitting stable Raman label signals for SERS liquid biopsy of pancreatic cancer

To develop a reliable surface-enhanced Raman scattering (SERS) immunoassay as a new liquid biopsy modality, SERS nanoprobes emitting strong and stable signals are necessary. However, Ag nanoparticles used as SERS nanoprobes are prone to rapid fading of SERS signals by oxidation. This has driven the development of a new strategy for Ag-based SERS nanoprobes emitting stable and strong SERS signals over time. Herein, Ag nanogap shells entrapping Raman labels are created in the confined pores of mesoporous silica nanoparticles (AgNSM) through a rapid single-step reaction for SERS liquid biopsy. Each AgNSM nanoprobe possesses multiple nanogaps of 1.58 nm to entrap Raman labels, allowing superior long-term SERS signal stability and large enhancement of 1.5 × 106. AgNSM nanoprobes conjugated with an antibody specific for carbohydrate antigen (CA)19-9 are employed in the SERS sandwich immunoassay including antibody-conjugated magnetic nanoparticles for CA19-9 detection, showing a two orders of magnitude lower limit of detection (0.025 U mL−1) than an enzyme-linked immunosorbent assay (0.3 U mL−1). The AgNSM nanoprobe immunoassay accurately quantifies CA19-9 levels from clinical serum samples of early and advanced pancreatic cancer. AgNSM nanoprobes with stable SERS signals provide a new route to SERS liquid biopsy for effective detection of blood biomarkers.

Contact Lens with pH Sensitivity for On-Demand Drug Release in Wearing Situation.

Drug-releasing contact lenses are emerging therapeutic systems for treating ocular diseases. However, their applicability is limited by the burst release of drugs during lens wear and premature drug leakage during packaging, rendering the precise control of release duration or dose difficult. Here, we introduce a pH-sensitive contact lens exhibiting on-demand drug release only during lens wear and negligible premature drug leakage during packaging and transportation, which is accomplished by incorporating drug-loaded mesoporous silica nanoparticles (MSNs) coated with a pH-sensitive polymer into the contact lens. The compositionally optimized pH-sensitive polymer has a lower critical solution temperature (LCST) at >45 °C at pH 7.4, whereas its LCST decreases to <35 °C under acidic conditions (pH ∼ 6.5). Consequently, the MSN-incorporated contact lens sustainably releases the loaded drugs only in the acidic state at 35 °C, which corresponds to lens-wear conditions, through the MSN pores that open because of the shrinkage of polymer chains. Conversely, negligible drug leakage is observed from the contact lens under low-temperature or neutral-pH conditions corresponding to packaging and transportation. Furthermore, compared with the plain contact lens, the pH-sensitive contact lens exhibits good biocompatibility and unchanged bulk characteristics, such as optical (transmittance in the visible-light region), mechanical (elastic modulus and tensile strength), and physical (surface roughness, oxygen permeability, and water content) properties. These findings suggest that the pH-sensitive contact lens can be potentially applied in ocular disease treatment.

Poly(2-n-propyl-2-oxazoline)/tannic acid nanocapsules with in-situ synthesized gold nanorods for cancer theranostics

The concept of hollow polymeric capsules fabricated with thermoresponsive polymers has revealed immense possibilities in the field of nanomedicine due to their tunable temperature and pH responsiveness caused by lower critical solution temperature (LCST) behavior. Herein, we report a new methodology to in-situ synthesize gold nanorods (AuNRs) within the pores of mesoporous silica nanoparticles (NPs) by trapping gold seed crystals and growing them into NRs in the presence of a weak reducing agent. The mesoporous silica NPs with incorporated NRs, i.e., modified silica NPs (SiO2-NRs) were used as sacrificial template for the fabrication of hollow polymeric multilayer capsules via layer-by-layer (LbL) assembly using poly(2-n-propyl-2-oxazoline) (PnPrOx) and tannic acid (TA) as layer components. The NRs of 25 ± 5 nm in size were uniformly distributed in the interior structure of PnPrOx/TA nanocapsules. The photo-thermal conversion efficiency of the PnPrOx/TA nanocapsules was found to be 47.5%. The release of encapsulated doxorubicin was found to be 55%, which increased to 68% when the incubation time was increased from 1 to 2 h. An on-demand burst release of 56% of the drug occurred within 2 min of NIR light exposure, and it reached 72% within 30 min, which inflicted major damage to cancer cells. Notably, the capsule suspension temperature increase from room temperature to 47 °C under laser light exposure, which is not only playing a key role in rupturing the capsules to enhance the drug release but also induces a hyperthermia effect in the tumor environment. Further, the in-vitro cytotoxicity experiments with human epithelial HEp-2 cells and fibrosarcoma HT1080 cells revealed an enhanced anti-cancer activity due to a synergistic chemo-photothermal effect. Hence, the proposed nanocapsule system can provide a unique, cheap, and efficient way of fabricating cancer theranostics for in-vivo applications.

Injectable Hydrogel Containing Bupivacaine-Loaded Mesoporous Silica Nanoparticles for Local Anesthetic Therapy

Developing a sustained drug delivery system with effective administration ruts is a central demand for local anesthesia applications. Moreover, the fast systemic absorption of the approved local anesthetics due to their low molecular weight have highlighted these demand. The main objective of the current study is to develop a sustained drug delivery system with effective administration ruts based on the combination of injectable hydrogel with mesoporous silica nanoparticles (MSNPs). The MSNPs were synthesized by combining the one-pot sol-gel reaction and the templating micelle system. Bupivacaine was loaded into the pores of MSNPs, and the nanoparticles were characterized using DLS, Zetasizer, SEM, TEM, encapsulation efficacy and drug loading capacity. The synthesized bupivacaine-loadedMSNPs were incorporated into a hydrogel based on alginate and characterized. The characterizations revealed that the formulation exhibited proper physicochemical properties beneficial for injectable hydrogel applications. The biological studies showed excellent encapsulation efficacy, drug loading efficacy, and local anesthetic effects. In conclusion, these results showed that the synthesized injectable hydrogel containing bupivacaine-loaded MSNPs could be considered an effective drug delivery system for local anesthetic therapy.

Stimulus-responsive strategy based on MnO2 nanosheet-modified mesoporous silica nanoprobes for accurate multiple mRNAs detection

Fluorescence detection of multiple mRNAs has attracted great attention for disease diagnosis. In this work, a stimulus-responsive strategy for highly sensitive and accurate multiple mRNAs detection was proposed. This stimulus-responsive detection system was prepared by mesoporous silica nanoparticles (MSN), manganese dioxide (MnO2) nanosheets, and DNA probes. DNA probes were loaded into the pores of MSN, which were closed with MnO2 nanosheets. In the presence of glutathione (GSH) and target mRNAs, MnO2 nanosheets were degraded by GSH, resulting in the release of DNA probes. These DNA probes hybridized to the corresponding target mRNA, thereby changing the fluorescence intensity of fluorophores of DNA probes, which could achieve the quantification of target mRNA. This system could simultaneously detect survivin mRNA and Thymidine kinase 1 mRNA at low background levels with relative limits of detection of 0.9 nM and 0.7 nM, respectively. Moreover, this assay has been successfully applied to detect multiple mRNAs with adequate anti-interference ability in the biological sample.

Abstract 2458: Comparing influences of active targeting and nanoparticle size on tumor specificity in pancreatic adenocarcinoma

Abstract Purpose: While nanoparticles are widely studied as potential theranostic treatments for cancer, weak tumor specificity has hindered clinical translation. Features that contribute to tumor specificity are historically controversial, particularly when using clinically relevant models. Aggressive cancers, such as pancreatic ductal adenocarcinoma (PDAC), stand to benefit from development of highly specific nanoparticles as a theranostic drug delivery system. This work evaluates active targeting and nanoparticle size, in a silica-based nanoparticle for specific accumulation and release of contrast agent within an orthotopically implanted tumor. Methods: Mesoporous silica nanoparticles (MSNs) were synthesized with wormhole-like pores using a silica precursor to coat a surfactant scaffold. Chitosan was attached to MSN surface as a pH-responsive gatekeeper for encapsulated agents. A series of acidification and basification procedures resulted in loading of photoacoustic contrast agent IR780 within MSN pores. MSNs were further functionalized for attachment of V7 peptide to target aggressive and acidic pancreatic cancer. pH-sensitivity and tumor specificity/uptake was validated using an in vitro PDAC cell model (S2VP10L) prior to implantation and assessment in an animal model. Functionalized MSNs were intravenously injected into athymic mice with orthotopically implanted PDAC tumors. Near infrared fluorescence and optoacoustic imaging were used to evaluate the biodistribution of MSNs subsequent to treatment. Results: Zeta potential, DLS, and TEM were utilized to show three differently sized MSNs of 26, 45, and 73 nm and confirm conjugation of chitosan and V7 peptide. Dye-release assays indicated significantly increased agent release from MSNs in acidic pH (~90%) compared to biological pH (~15%) (p=0.001). Treatment of PDAC cell line with MSNs showed highest uptake and specificity with actively targeted 26nm particles and that all actively targeted MSNs exhibited greater specificity than all passively targeted MSNs (p&amp;lt;0.05). In vivo results utilizing optoacoustic imaging confirmed that active targeting produces a stronger tumor specificity, and that nanoparticle size has a secondary influence in which the smaller, 26 nm MSNs, showed optimal specificity (p&amp;lt;0.001). Ex vivo evaluation of organs was in agreement with in vivo observations. Conclusion: Active targeting outperforms nanoparticle size for facilitation of tumor-specific uptake in an acidic PDAC murine model. Active targeting was necessary for high accumulation of MSNs and contrast agent in the tumor. Nanoparticle size had a secondary, but notable influence on tumor uptake in which smaller sized MSNs resulted in higher tumor specificity. Citation Format: William M. MacCuaig, Abhilash Samykutty, Molly McNally, Ajay Jain, William E. Grizzle, Lacey R. McNally. Comparing influences of active targeting and nanoparticle size on tumor specificity in pancreatic adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2458.

Drug delivery system with dual imaging and dual response control drug release functions for chemo-photodynamic synergistic therapy

Traditional treatment of cancers such as chemotherapy still causes many side effects after the treatment even nowadays, therefore combination therapies by using drug delivery systems are valued by more and more scientists. However, loading multiple drugs in the nanoparticles for drug delivery system may cause insufficient drugs or functional groups, which might let the nanomaterial have fewer functions. Therefore, making the mesoporous silica nanoparticles (MSNs) have photodynamic therapy function by “doping “ lanthanide ions into the material structure, can evade this problem. Moreover, with the doping of lanthanide metals, the MSNs can have not only dual imaging functions of both magnetic resonance imaging and fluorescence, but also achieve photodynamic function. To feature the material with more function, chemotherapeutic drug-doxorubicin was loaded into the pores of MSNs and then bonded hyaluronic acid which is the active target and a gatekeeper, on the surface of MSNs. Finally, an all-in-one drug delivery system” Hyaluronidase and pH-responsive mesoporous silica nanoparticles with dual-imaging activity for chemo-photodynamic therapy” is synthesized. The first part in this experiment was to confirm the physical properties of the lanthanides dopped MSN and its photodynamic treatment effect. The second part was to confirm that each organic molecule had been successfully bonded to the surface of the MSN and achieve pH and Hyaluronidase response drug release effect, The last part was to prove that the drug delivery system had a significant anticancer effect through cell experiments.

Mesoporous silica nanospheres supported atomically precise palladium nanocluster: Highly efficient and recyclable catalysts in the reduction of 4‐nitrophenol and Heck reactions

AbstractAtomically precise palladium nanoclusters show great potential applications in the field of catalysis owing to its ultrasmall size and precise structure. This work, we report the mesoporous silica nanoparticles (MSNs) supported [Pd3Cl(PPh3)3(PPh2)2]Cl catalysts (denoted as Pd3Cl/MSNs) for the reduction of 4‐nitrophenol and Heck coupling reactions of iodobenzene and styrenes. High uniform MSNs, with average diameter ≈110 nm, were prepared by sol–gel method, followed by Pd nanoclusters immobilization into the pore of MSNs. The MSNs supported Pd nanoclusters were well characterized by X‐ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), X‐ray photoelectron spectroscopy (XPS), Fourier transform infrared (FT‐IR), and diffuse reflectance optical spectrum. The results indicated that Pd3Cl nanoclusters after immobilized into the pores of MSNs are intact and possess good dispersibility. The catalytic performance of as‐prepared nanocomposites was evaluated by the reduction of 4‐nitrophenol and Heck reactions. The 4‐nitrophenol could be completely conversion to 4‐aminophenol within 6 min. Meanwhile, the as‐prepared Pd3Cl/MSNs exhibit excellent catalytic performance in the Heck reactions between iodobenzenes and styrenes. The high catalytic activity of Pd3Cl/MSNs could be attributed to the large surface area and unique geometric structure of as‐prepared Pd nanoclusters. More importantly, the catalysts could be easily recycled by centrifugation and shows excellent reusability.

Synthesis of Pore-Size-Tunable Mesoporous Silica Nanoparticles by Simultaneous Sol-Gel and Radical Polymerization to Enhance Silibinin Dissolution.

Background: Silibinin (SBN), a major active constituent of milk thistle seeds, exhibits numerous pharmacological activities. However, its oral bioavailability is low due to poor water solubility. This study aimed to develop a new synthetic approach for tuning the pore characteristics of mesoporous silica nanoparticles (MSNs) intended for the oral delivery of SBN. In addition, the effects of the pore diameter of MSNs on the loading capacity and the release profile of SBN were investigated.Methods: The present study was performed at Shiraz University of Medical Sciences, Shiraz, Iran, in 2019. This synthesis method shares the features of the simultaneous free-radical polymerization of methyl methacrylate and the sol-gel reaction of the silica precursor at the n-heptane/water interface. SBN was loaded onto MSNs, the in vitro release was determined, and the radical scavenging activities were compared between various pH values using the analysis of variance.Results: According to the Brunauer–Emmett–Teller protocol, the pore sizes were well-tuned in the range of 2 to 7 nm with a large specific surface area (600–1200 m2/g). Dynamic light scattering results showed that different volume ratios of n-heptane/water resulted in different sizes, ranging from 25 to 100 nm. Interestingly, high SBN loading (13% w/w) and the sustained release of the total drug over 12 hours were achieved in the phosphate buffer (pH=6.8). Moreover, the antioxidant activity of SBN was well preserved in acidic gastric pH.Conclusion: Well-tuned pores of MSNs provided a proper substrate, and thus, enhanced SBN loading and oral dissolution and preserved its antioxidant activity. Nevertheless, further in vitro and in vivo investigations are needed.

Mesoporous Silica Nanoprodrug Encapsulated with Near-Infrared Absorption Dye for Photothermal Therapy Combined with Chemotherapy.

Based on the tumor microenvironment with weak acidic characteristics, a nano-drug delivery system that achieves controlled release of drugs through the pH response has been a popular strategy to improve the effectiveness of tumor therapy and reduce toxic side effects, and combining photothermal therapy (PTT) on this basis can help improve the antitumor effect. In this study, mesoporous silica nanoparticles (MSNs) were surface-modified with polymer poly(PEGMA-co-HEMA) via surface-initiated atom transfer radical polymerization, and a multifunctional nanoplatform MSN@poly(PEGMA-co-HEMA-g-doxorubicin (DOX)/indocyanine green (ICG) was designed for effective photothermal/chemotherapy combination therapy. The anticancer drug DOX was anchored to the polymer on the surface of MSN by reversible covalent bond cis-aconitic anhydride with a drug loading of 10%. Meanwhile, the small-molecule dye was loaded into the pores of MSN, and PTT mediated by near-infrared (NIR) radiation could further kill cancer cells. Under low-pH stimulation, the cis-aconitic anhydride bond breaks and DOX is released, with a 65% increase in cumulative drug release over 50 h compared to that at pH 7.4 (normal physiological environment). The high temperature induced by photothermal conversion accelerated the reversible covalent bond breakage, and the cumulative drug release at pH 5.0 for 3 h at elevated temperature up to 50 °C increased by 24.3% compared with that under normal physiological conditions (T = 37 °C), demonstrating that increasing the temperature can reduce the time required to reach blood drug concentration. In vitro cytotoxicity results revealed that the prodrug delivery system showed stronger cytotoxicity under NIR light irradiation compared with free DOX, with more than 90% of tumor cells killed after 48 h. Therefore, MSN@poly(PEGMA-co-HEMA-g-DOX)/ICG enhanced the synergistic effect of chemotherapy through photothermal action and accelerated reversible chemical bond cleavage, which has great potential in the combined therapy of cancer.

Efficiency of mesoporous silica/carboxymethyl β-glucan as a fungicide nano-delivery system for improving chlorothalonil bioactivity and reduce biotoxicity

Understanding the lethal effects of pesticides nano formulations on the targeted organisms (pathogens) and the non-targeted organisms (fish, earthworms, etc) is essential in assessing the probable impact of new technologies on agriculture and environment. Here we evaluated the bioactivity and the biotoxicity of new type of fungicide smart-delivery formulation based on conjugating carboxymethylated-β-glucans on the mesoporous silica nanoparticles (MSNs) surface after loading chlorothalonil (CHT) fungicide in the MSNs pores. The obtained formulation has been characterized with FE-SEM, and HR-TEM. The CHT loading efficiency has been measured with TGA. The bioactivity of the obtained formulation (CHT@MSNs-β-glucans) has been tested against four pathogens, fusarium head blight (Fusarium graminearum), sheath rot (Sarocladium oryzae), rice sheath blight (Rhizoctonia solani), and soyabean anthracnose (Colletotrichum truncatum) compared with CHT WP 75% commercial formulation (CHT-WP) and technical CHT. The environmental biotoxicity of CHT@MSNs-β-glucans compared with CHT-WP has been tested toward earthworm (Eisenia fetida) and zebra fish (Danio rerio). The results showed that CHT@MSNs-β-glucans has an excellent bioactivity against the subjected pathogens with better inhabiting effects than CHT-WP. CHT@MSNs-β-glucans toxicity to Eisenia fetida was found 2.25 times lower than CHT-WP toxicity. The LC50 of CHT@MSNs-β-glucans to zebra fish after the first 24h was 2.93 times higher than CHT-WP. After 96h of treatment, the LC50 of CHT@MSNs-β-glucans was 2.66 times higher than CHT-WP. This work highlighted the necessity to increase the mandatory bioassays of nano formulations with the major non-target organisms in the environmental risk assessment of new pesticide formulations.

SERS Sensors Based on Aptamer-Gated Mesoporous Silica Nanoparticles for Quantitative Detection of Staphylococcus aureus with Signal Molecular Release.

This work describes a simple and novel biosensor for the quantitative determination of Staphylococcus aureus (S. aureus) based on target-induced release of signal molecules from aptamer-gated aminated mesoporous silica nanoparticles (MSNs) coupled with surface-enhanced Raman scattering (SERS) technology. MSNs were synthesized and then modified with amino groups by (3-aminopropyl) triethoxysilane to make them positively charged. Next, signal molecules (4-aminothiophenol, 4-ATP) were loaded into the pores of MSNs. Then, negatively charged aptamers of S. aureus were assembled on the surface of MSNs through electrostatic interactions. Upon the addition of S. aureus, the assembled aptamers were specifically bound to the bacteria. Consequently, the "gates" were opened, resulting in the release of 4-ATP from the pores of MSNs. The released molecules were measured by a Raman spectrometer, and the intensity of 4-ATP at 1071 cm-1 was linearly related to the S. aureus concentration. A silver nanoflower silica core-shell structure (Ag NFs@SiO2) was prepared and it served as a SERS substrate. Under optimized experimental conditions, a good linear relationship (y = 2107.93 + 1536.30x, R2 = 0.9956) in the range from 4.7 × 10 to 4.7 × 108 cfu/mL was observed with a limit of detection of 17 cfu/mL. The method was successfully applied for the analysis of S. aureus in fish samples and the recovery rate was 91.3-109%.

Development of mesoporous silica-based nanoprobes for optical bioimaging applications.

A mesoporous silica nanoparticle (MSN)-based nanoplatform has attracted growing attention in the biomedical field due to the unique characteristics of MSNs including a high surface area, tunable pore sizes, colloidal stability, ease of functionalization, and desirable biocompatibility. Typically, MSNs are designed as nanocarriers for the incorporation of a variety of contrast agents for bioimaging, which can address the intrinsic drawbacks of contrast agents, including poor solubility in water, rapid photobleaching, and low stability. This review summarizes the recent advances in the field of MSN-based nanoprobes for fluorescence imaging and photoacoustic (PA) imaging applications. The approaches for the incorporation of contrast agents into MSN-based nanoplatforms including encapsulating contrast agents within MSNs, covalently conjugating contrast agents on the surface or pores of MSNs, physically absorbing contrast agents in the pores of MSNs, and doping contrast agents in the framework of MSNs are introduced. MSN-based nanoprobes for fluorescence imaging and PA imaging are discussed. The enhanced fluorescence imaging and PA imaging performances of MSN-based nanoprobes relative to the bare contrast agents are introduced and the underlying mechanisms are discussed in detail. Finally, current challenges and perspectives of MSN-based nanoprobes in the bioimaging field are discussed.

Regulating the Catalytic Activity of Pd Nanoparticles by Confinement in Ordered Mesoporous Supports

AbstractStudying structure‐sensitive reactions requires the synthesis of catalytic nanoparticles with precisely controlled sizes. In this work we demonstrate the facile production of size controlled Pd nanoparticles by confinement in the pores of mesoporous silica nanoparticles (MSN). We show that Pd particles 2.1 nm in size have a higher catalytic activity than larger nanoparticles for the Suzuki‐Miyaura cross‐coupling between 4’‐bromoacetophenone and phenyl boronic acid and for the hydrogenation of phenol in aqueous phase. The enhanced activity can be explained in terms of increased number of coordinatively unsaturated sites and higher back donation capacity of the small nanoparticles.

Modification of Mesoporous Silica Surface by Immobilization of Functional Groups for Controlled Drug Release

This paper introduces the synthesis of mesoporous silica nanoparticles (MSNs) with three different groups such as amine, thiol, and sulfonic acid, along the internal surface. Trimethyl[3-(trimethoxysilyl)propyl]ammonium chloride was used to modify the external surface of the nanomaterials. Such materials allow control of the drug release from MSN pores. Multifunctional MSNs were loaded with doxycycline (Doxy) to study their capacities and uploading time. The loading profile indicates that sulfonic groups in the internal surface were the most efficient surfaces with a loading capacity of ca. 35% in 90 min in acidic media.

Prodrug-Based Nanoreactors with Tumor-Specific In Situ Activation for Multisynergistic Cancer Therapy

Efficient drug delivery into tumor cells while bypassing many biological barriers is still a challenge for cancer therapy. By taking advantage of the palladium (Pd)-mediated in situ activation of a prodrug and the glucose oxidase (GOD)-based β-d-glucose oxidation reaction, we developed a multisynergistic cancer therapeutic platform that combined doxorubicin (DOX)-induced chemotherapy with GOD-mediated cancer-orchestrated oxidation therapy and cancer starvation therapy. In the present work, we first synthesized DOX prodrugs (pDOXs) and temporarily assembled them with β-cyclodextrins to reduce their toxic side effects. Then, a nanoreactor was constructed by synthesizing Pd0 nanoparticles in situ within the pores of mesoporous silica nanoparticles for the conversion of pDOX into the active anticancer drug. Furthermore, GOD was introduced to decrease the pH of the tumor microenvironment and induce cancer-orchestrated oxidation/starvation therapy by catalyzing β-d-glucose oxidation to form hydrogen peroxide (H2O2) and gluconic acid. Our study provides a new strategy that employs a cascade chemical reaction to achieve combined orchestrated oxidation/starvation/chemotherapy for the synergistic killing of cancer cells and the suppression of tumor growth.