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Jeffrey C Brinker - One of the best experts on this subject based on the ideXlab platform.

  • conversion of metal organic cage to ligand free ultrasmall noble metal nanocluster catalysts confined within Mesoporous Silica Nanoparticle supports
    Nano Letters, 2019
    Co-Authors: Wei Zhu, Jeffrey C Brinker, Achraf Noureddine, Jane Y. Howe, Jimin Guo
    Abstract:

    Supported ultrasmall noble metal nanocluster-based (UNMN-based) catalysts are one of the most important classes of solid materials for heterogeneous catalysis. In this work, we present a novel strategy for the controlled synthesis of ligand-free UNMN nanocatalysts based on in situ reduction of a palladium-based (Pd-based) metal-organic cage (MOC) confined within monosized, thiol-modified Mesoporous Silica Nanoparticle (MSN) supports. By taking advantage of the high mutual solubility of MOCs and MSNs in DMSO and the strong interactions between the thiol-modified MSN pore wall and MOC surface, a good dispersion of MOC molecules was achieved throughout the MSN support. The close correspondence of the MSN pore diameter (ca. 5.0 nm) with the diameter of the MOC (ca. 4.0 nm) confines MOC packing to approximately a monolayer. Based on this spatial constraint and electrostatic binding of the MOC to the thiol-modified MSN pore surface, in situ MOC reduction followed by metal atom diffusion, coalescence, and anchoring on the active sites resulted in ligand-free Pd-based UNMNs of approximately 0.9 ± 0.2 nm in diameter decorating the MSN pore surfaces. Control experiments of the reduction of a conventional palladium source or the reduction of free, unconstrained cages in solution under the same conditions only produced large metal nanocrystals (NP, >2 nm), confirming the importance of confined reduction to achieve a highly catalytically active surface. In light of this strategy, two catalytic experiments including the reaction of 4-nitrophenol to 4-aminophenol and the Suzuki C-C coupling reaction show superior catalytic activity of the engineered MSN-supported UNMN nanocatalysts compared to their free form and state of the art commercial catalysts. We believe that our new strategy will open new avenues for artificially designed UNMN-inspired nanoarchitectures for wide applications.

  • Conversion of Metal–Organic Cage to Ligand-Free Ultrasmall Noble Metal Nanocluster Catalysts Confined within Mesoporous Silica Nanoparticle Supports
    2019
    Co-Authors: Wei Zhu, Achraf Noureddine, Jane Y. Howe, Jimin Guo, Jeffrey C Brinker
    Abstract:

    Supported ultrasmall noble metal nanocluster-based (UNMN-based) catalysts are one of the most important classes of solid materials for heterogeneous catalysis. In this work, we present a novel strategy for the controlled synthesis of ligand-free UNMN nanocatalysts based on in situ reduction of a palladium-based (Pd-based) metal–organic cage (MOC) confined within monosized, thiol-modified Mesoporous Silica Nanoparticle (MSN) supports. By taking advantage of the high mutual solubility of MOCs and MSNs in DMSO and the strong interactions between the thiol-modified MSN pore wall and MOC surface, a good dispersion of MOC molecules was achieved throughout the MSN support. The close correspondence of the MSN pore diameter (ca. 5.0 nm) with the diameter of the MOC (ca. 4.0 nm) confines MOC packing to approximately a monolayer. Based on this spatial constraint and electrostatic binding of the MOC to the thiol-modified MSN pore surface, in situ MOC reduction followed by metal atom diffusion, coalescence, and anchoring on the active sites resulted in ligand-free Pd-based UNMNs of approximately 0.9 ± 0.2 nm in diameter decorating the MSN pore surfaces. Control experiments of the reduction of a conventional palladium source or the reduction of free, unconstrained cages in solution under the same conditions only produced large metal nanocrystals (NP, >2 nm), confirming the importance of confined reduction to achieve a highly catalytically active surface. In light of this strategy, two catalytic experiments including the reaction of 4-nitrophenol to 4-aminophenol and the Suzuki C–C coupling reaction show superior catalytic activity of the engineered MSN-supported UNMN nanocatalysts compared to their free form and state of the art commercial catalysts. We believe that our new strategy will open new avenues for artificially designed UNMN-inspired nanoarchitectures for wide applications

  • uptake and intracellular fate of cholera toxin subunit b modified Mesoporous Silica Nanoparticle supported lipid bilayers aka protocells in motoneurons
    Nanomedicine: Nanotechnology Biology and Medicine, 2018
    Co-Authors: Maria Gonzalez A Porras, Paul N Durfee, Jeffrey C Brinker, Sebastian Giambini, Gary C Sieck, Carlos B Mantilla
    Abstract:

    Cholera toxin B (CTB) modified Mesoporous Silica Nanoparticle supported lipid bilayers (CTB-protocells) are a promising, customizable approach for targeting therapeutic cargo to motoneurons. In the present study, the endocytic mechanism and intracellular fate of CTB-protocells in motoneurons were examined to provide information for the development of therapeutic application and cargo delivery. Pharmacological inhibitors elucidated CTB-protocells endocytosis to be dependent on the integrity of lipid rafts and macropinocytosis. Using immunofluorescence techniques, live confocal and transmission electron microscopy, CTB-protocells were primarily found in the cytosol, membrane lipid domains and Golgi. There was no difference in the amount of motoneuron activity dependent uptake of CTB-protocells in neuromuscular junctions, consistent with clathrin activation at the axon terminals during low frequency activity. In conclusion, CTB-protocells uptake is mediated principally by lipid rafts and macropinocytosis. Once internalized, CTB-protocells escape lysosomal degradation, and engage biological pathways that are not readily accessible by untargeted delivery methods.

  • protocells modular Mesoporous Silica Nanoparticle supported lipid bilayers for drug delivery
    Small, 2016
    Co-Authors: Kimberly S Butler, Paul N Durfee, Christophe Theron, Carlee E Ashley, Eric C Carnes, Jeffrey C Brinker
    Abstract:

    Mesoporous Silica Nanoparticle-supported lipid bilayers, termed ‘protocells,’ represent a potentially transformative class of therapeutic and theranostic delivery vehicle. The field of targeted drug delivery poses considerable challenges that cannot be addressed with a single ‘magic bullet’. Consequently, the protocell has been designed as a modular platform composed of interchangeable biocompatible components. The Mesoporous Silica core has variable size and shape to direct biodistribution and a controlled pore size and surface chemistry to accommodate diverse cargo. The encapsulating supported lipid bilayer can be modified with targeting and trafficking ligands as well as polyethylene glycol (PEG) to effect selective binding, endosomal escape of cargo, drug efflux prevention, and potent therapeutic delivery, while maintaining in vivo colloidal stability. This review describes the individual components of the platform, including the Mesoporous Silica Nanoparticle core and supported lipid bilayer, their assembly (by multiple techniques) into a protocell, and the combined, often synergistic, performance of the protocell based on in vitro and in vivo studies, including the assessment of biocompatibility and toxicity. In closing, the many emerging variations of the protocell theme and the future directions for protocell research are commented on.

  • two wave nanotherapy to target the stroma and optimize gemcitabine delivery to a human pancreatic cancer model in mice
    ACS Nano, 2013
    Co-Authors: Huan Meng, Jeffrey C Brinker, Yushen Lin, Haiyuan Zhang, Chong Hyun Chang, Juyao Dong, Yang Zhao, Min Xue, Wilson X Mai, Jeffrey I Zink
    Abstract:

    Pancreatic ductal adenocarcinoma (PDAC) elicits a dense stromal response that blocks vascular access because of pericyte coverage of vascular fenestrations. In this way, the PDAC stroma contributes to chemotherapy resistance in addition to causing other problems. In order to improve the delivery of gemcitabine, a first-line chemotherapeutic agent, a PEGylated drug-carrying liposome was developed, using a transmembrane ammonium sulfate gradient to encapsulate the protonated drug up to 20% w/w. However, because the liposome was precluded from entering the xenograft site due to the stromal interference, we developed a first-wave nanocarrier that decreases pericyte coverage of the vasculature through interference in the pericyte recruiting TGF-β signaling pathway. This was accomplished using a polyethyleneimine (PEI)/polyethylene glycol (PEG)-coated Mesoporous Silica Nanoparticle (MSNP) for molecular complexation to a small molecule TGF-β inhibitor, LY364947. LY364947 contains a nitrogen atom that attaches, t...

Xianzheng Zhang - One of the best experts on this subject based on the ideXlab platform.

  • super ph sensitive Mesoporous Silica Nanoparticle based drug delivery system for effective combination cancer therapy
    ACS Biomaterials Science & Engineering, 2019
    Co-Authors: Yinjia Cheng, Siyong Qin, Xiaosui Chen, Aiqing Zhang, Xianzheng Zhang
    Abstract:

    A multifunctional nanoplatform based on Mesoporous Silica Nanoparticles (MSNs) was developed for combinational tumor therapy. Doxorubicin (DOX) was chosen as an antitumor drug and loaded into mesopores of MSNs via physical absorption. Then, a tumor-targeted fusion peptide conjugated with 2,3-dimethylmaleic anhydride (DTCPP) and a therapeutic peptide conjugated with 2,3-dimethylmaleic anhydride (DTPP) were introduced to the surface of MSNs as super-pH-sensitive nanovalves through disulfide linkages. The BSA adsorption assay confirmed the charge-reversal property of MSN-ss-DTPP&DTCPP Nanoparticles at slightly acidic condition (pH 6.8) and superior stability in physiological environment (pH 7.4). According to the drug release research, both glutathione (GSH) and acidic condition are required for the accelerated drug release from DOX@MSN-ss-DTPP&DTCPP Nanoparticles. Moreover, in vitro studies demonstrated the significantly reinforced tumor cellular uptake efficiency and mitochondrial disruption ability of DOX...

  • a redox responsive Mesoporous Silica Nanoparticle with a therapeutic peptide shell for tumor targeting synergistic therapy
    Nanoscale, 2016
    Co-Authors: Dong Xiao, Renxi Zhuo, Jingyi Zhu, Shibo Wang, Xianzheng Zhang
    Abstract:

    In this study, we report a novel redox-responsive Mesoporous Silica Nanoparticle (MSN)-based nanocarrier, capping with a therapeutic peptide ((RGDWWW)2KC) containing a RGD target motif, for tumor targeting synergistic therapy, which is designated as TTSTMSN. The MSN was decorated with a tumor-targeting therapeutic peptide as a potential gatekeeper. The two branched peptides containing rich tryptophans allowed the pores to be blocked via π-π stacking and hydrophobic interactions. Once the drug loaded Nanoparticles were taken up by the cancer cells through integrin-mediated endocytosis, the therapeutic peptide capping shells on the surface of MSNs were released, inducing the loaded drug to diffuse into the cytoplasm after breaking of the disulfide bonds, triggered by the high concentration of glutathione (GSH) in cancer cells. At the same time, the falling therapeutic rich tryptophans in the branched chains interacted with DNA due to the indole rings, leading to disturbance of the DNA structure through the strong π interactions and causing cell apoptosis. There is no such report on capping of drug loaded porous Silica with a therapeutic peptide shell, co-delivering an anticancer drug and therapeutic agent for tumor targeting synergistic therapy, which will have great potential in developing multifunctional nanocarriers based on therapeutic peptides for synergistic treatment.

  • multifunctional Mesoporous Silica Nanoparticles with thermal responsive gatekeeper for nir light triggered chemo photothermal therapy
    Small, 2016
    Co-Authors: Qi Lei, Wenxiu Qiu, Pengxi Cao, Chenghui Zhu, Han Cheng, Xianzheng Zhang
    Abstract:

    In this work, a matrix metalloproteinase (MMP)-triggered tumor targeted Mesoporous Silica Nanoparticle (MSN) is designed to realize near-infrared (NIR) photothermal-responsive drug release and combined chemo/photothermal tumor therapy. Indocyanine green (ICG) and doxorubicin (DOX) are both loaded in the MSN modified with thermal-cleavable gatekeeper (Azo-CD), which can be decapped by ICG-generated hyperthermia under NIR illumination. A peptidic sequence containing a short PEG chain, matrix metalloproteinase (MMP) substrate (PLGVR) and tumor cell targeting motif (RGD) are further decorated on the MSN via a host-guest interaction. The PEG chain can protect the MSN during the circulation and be cleaved off in the tumor tissues with overexpressed MMP, and then the RGD motif is switched on to target tumor cells. After the tumor-triggered targeting process, the NIR irradiation guided by ICG fluorescence can trigger cytosol drug release and realize combined chemo/photothermal therapy.

  • a redox responsive Mesoporous Silica Nanoparticle capped with amphiphilic peptides by self assembly for cancer targeting drug delivery
    Nanoscale, 2015
    Co-Authors: Dong Xiao, Huizhen Jia, Renxi Zhuo, Xianzheng Zhang
    Abstract:

    A redox-responsive Mesoporous Silica Nanoparticle (RRMSN) was developed as a drug nanocarrier by noncovalent functionalization of MSNs with amphiphilic peptides containing the RGD ligand. The alkyl chain stearic acid (C18) with a thiol terminal group was anchored on the surface of MSNs via a disulfide bond, and the amphiphilic peptide (AP) C18-DSDSDSDSRGDS was coated by self-assembly through hydrophobic interactions between the octadecyl groups of MSNs and alkyl chains of AP, which played the role of a gatekeeper collectively. In vitro drug release profiles demonstrated that the anticancer drug (DOX) could be entrapped with nearly no leakage in the absence of dithiothreitol (DTT) or glutathione (GSH). With the addition of DTT or GSH, the entrapped drug released quickly due to the cleavage of the disulfide bond. It was found that after the internalization of MSNs by cancer cells via the receptor-mediated endocytosis, the surface amphiphilic peptides and alkyl chain of RRMSN/DOX were removed to induce rapid drug release intracellularly after the cleavage of the disulfide bond, triggered by GSH secreted in cancer cells. This novel intelligent RRMSN/DOX drug delivery system using self-assembly of amphiphilic peptides around the MSNs provides a facile, but effective strategy for the design and development of smart drug delivery for cancer therapy.

  • a redox responsive drug delivery system based on rgd containing peptide capped Mesoporous Silica Nanoparticles
    Journal of Materials Chemistry B, 2015
    Co-Authors: Si Chen, Huizhen Jia, Renxi Zhuo, Yunxia Sun, Xianzheng Zhang
    Abstract:

    In this paper, an intracellular glutathione (GSH) responsive Mesoporous Silica Nanoparticle (MSN-S-S-RGD) was developed as a drug nanocarrier by immobilizing the gatekeeper (RGD containing peptide) onto MSNs using disulfide bonds. The antitumor drug, DOX was loaded onto the porous structure of the MSNs and the DOX@MSN-S-S-RGD system has been proved to be an effective nanocarrier. It was determined that most of the drug could be entrapped with only a slight leakage. After being accumulated in tumor cells via the receptor-mediated endocytosis, the surface peptide layer of DOX@MSN-S-S-RGD was removed to trigger the release of the entrapped drug to kill the tumor cell due to the cleavage of the disulfide bonds by intracellular GSH.

Jeffrey I Zink - One of the best experts on this subject based on the ideXlab platform.

  • a responsive Mesoporous Silica Nanoparticle platform for magnetic resonance imaging guided high intensity focused ultrasound stimulated cargo delivery with controllable location time and dose
    Journal of the American Chemical Society, 2019
    Co-Authors: Chian Cheng, Wei Chen, Le Zhang, Jeffrey I Zink
    Abstract:

    Magnetic resonance imaging (MRI) is an essential modality for clinical diagnosis, and MRI-guided high-intensity focused ultrasound (MRgHIFU) is a powerful technology for targeted therapy. Clinical applications of MRgHIFU primarily utilize hyperthermia and ablation to treat cancerous tissue, but for drug delivery applications thermal damage is undesirable. A biofriendly MRgHIFU-responsive Mesoporous Silica Nanoparticle (MSN) platform that is stimulated within a physiological safe temperature range has been developed, reducing the possibility of thermal damage to the surrounding healthy tissues. Biocompatible polyethylene glycol (PEG) was employed to cap the pores of MSNs, and the release of cargo molecules by HIFU occurs without substantial temperature increase (∼4 °C). To visualize by MRI and measure the stimulated delivery in situ, a U.S. Food and Drug Administration (FDA)-approved gadolinium-based contrast agent, gadopentetate dimeglumine (Gd(DTPA)2-), was used as the imageable cargo. Taking advantage of the three-dimensional (3-D) imaging and targeting capabilities of MRgHIFU, the release of Gd(DTPA)2- stimulated by HIFU was pinpointed at the HIFU focal point in 3-D space in a tissue-mimicking gel phantom. The amount of Gd(DTPA)2- released was controlled by HIFU stimulation times and power levels. A positive correlation between the amount of Gd(DTPA)2- released and T1 was found. The MRgHIFU-stimulated cargo release was further imaged in a sample of ex vivo animal tissue. With this technology, the biodistribution of the nanocarriers can be tracked and the MRgHIFU-stimulated cargo release can be pinpointed, opening up an opportunity for future image-guided theranostic applications.

  • Mesoporous Silica Nanoparticle delivery of chemically modified sirna against twist1 leads to reduced tumor burden
    Nanomedicine: Nanotechnology Biology and Medicine, 2015
    Co-Authors: James Finlay, Jeffrey I Zink, Fuyuhiko Tamanoi, Cai M Roberts, Juyao Dong, Carlotta A Glackin
    Abstract:

    Abstract Growth and progression of solid tumors depend on the integration of multiple pro-growth and survival signals, including the induction of angiogenesis. TWIST1 is a transcription factor whose reactivation in tumors leads to epithelial to mesenchymal transition (EMT), including increased cancer cell stemness, survival, and invasiveness. Additionally, TWIST1 drives angiogenesis via activation of IL-8 and CCL2, independent of VEGF signaling. In this work, results suggest that chemically modified siRNA against TWIST1 reverses EMT both in vitro and in vivo . siRNA delivery with a polyethyleneimine-coated Mesoporous Silica Nanoparticle (MSN) led to reduction of TWIST1 target genes and migratory potential in vitro . In mice bearing xenograft tumors, weekly intravenous injections of the siRNA-Nanoparticle complexes resulted in decreased tumor burden together with a loss of CCL2 suggesting a possible anti-angiogenic response. Therapeutic use of TWIST1 siRNA delivered via MSNs has the potential to inhibit tumor growth and progression in many solid tumor types. From the Clinical Editor Tumor progression and metastasis eventually lead to patient mortality in the clinical setting. In other studies, it has been found that TWIST1, a transcription factor, if reactivated in tumors, would lead to downstream events including angiogenesis and result in poor prognosis in cancer patients. In this article, the authors were able to show that when siRNA against TWIST1 was delivered via Mesoporous Silica Nanoparticle, there was tumor reduction in an in-vivo model. The results have opened up a new avenue for further research in this field.

  • two wave nanotherapy to target the stroma and optimize gemcitabine delivery to a human pancreatic cancer model in mice
    ACS Nano, 2013
    Co-Authors: Huan Meng, Jeffrey C Brinker, Yushen Lin, Haiyuan Zhang, Chong Hyun Chang, Juyao Dong, Yang Zhao, Min Xue, Wilson X Mai, Jeffrey I Zink
    Abstract:

    Pancreatic ductal adenocarcinoma (PDAC) elicits a dense stromal response that blocks vascular access because of pericyte coverage of vascular fenestrations. In this way, the PDAC stroma contributes to chemotherapy resistance in addition to causing other problems. In order to improve the delivery of gemcitabine, a first-line chemotherapeutic agent, a PEGylated drug-carrying liposome was developed, using a transmembrane ammonium sulfate gradient to encapsulate the protonated drug up to 20% w/w. However, because the liposome was precluded from entering the xenograft site due to the stromal interference, we developed a first-wave nanocarrier that decreases pericyte coverage of the vasculature through interference in the pericyte recruiting TGF-β signaling pathway. This was accomplished using a polyethyleneimine (PEI)/polyethylene glycol (PEG)-coated Mesoporous Silica Nanoparticle (MSNP) for molecular complexation to a small molecule TGF-β inhibitor, LY364947. LY364947 contains a nitrogen atom that attaches, t...

  • Mesoporous Silica Nanoparticle nanocarriers biofunctionality and biocompatibility
    Accounts of Chemical Research, 2013
    Co-Authors: Derrick Tarn, Jeffrey I Zink, Eric C Carnes, Carlee Erin Ashley, Jeffrey C Brinker
    Abstract:

    The study of ordered Mesoporous Silica materials has exploded since their discovery by Mobil researchers 20 years ago. The ability to make uniformly sized, porous, and dispersible Nanoparticles using colloidal chemistry and evaporation-induced self-assembly has led to many applications of Mesoporous Silica Nanoparticles (MSNPs) as "nanocarriers" for delivery of drugs and other cargos to cells. The exceptionally high surface area of MSNPs, often exceeding 1000 m²/g, and the ability to independently modify pore size and surface chemistry, enables the loading of diverse cargos and cargo combinations at levels exceeding those of other common drug delivery carriers such as liposomes or polymer conjugates. This is because noncovalent electrostatic, hydrogen-bonding, and van der Waals interactions of the cargo with the MSNP internal surface cause preferential adsorption of cargo to the MSNP, allowing loading capacities to surpass the solubility limit of a solution or that achievable by osmotic gradient loading. The ability to independently modify the MSNP surface and interior makes possible engineered biofunctionality and biocompatibility. In this Account, we detail our recent efforts to develop MSNPs as biocompatible nanocarriers (Figure 1 ) that simultaneously display multiple functions including (1) high visibility/contrast in multiple imaging modalities, (2) dispersibility, (3) binding specificity to a particular target tissue or cell type, (4) ability to load and deliver large concentrations of diverse cargos, and (5) triggered or controlled release of cargo. Toward function 1, we chemically conjugated fluorescent dyes or incorporated magnetic Nanoparticles to enable in vivo optical or magnetic resonance imaging. For function 2, we have made MSNPs with polymer coatings, charged groups, or supported lipid bilayers, which decrease aggregation and improve stability in saline solutions. For functions 3 and 4, we have enhanced passive bioaccumulation via the enhanced permeability and retention effect by modifying the MSNP surfaces with positively charged polymers. We have also chemically attached ligands to MSNPs that selectively bind to receptors overexpressed in cancer cells. We have used encapsulation of MSNPs within reconfigurable supported lipid bilayers to develop new classes of responsive nanocarriers that actively interact with the target cell. Toward function 4, we exploit the high surface area and tailorable surface chemistry of MSNPs to retain hydrophobic drugs. Finally, for function 5, we have engineered dynamic behaviors by incorporating molecular machines within or at the entrances of MSNP pores and by using ligands, polymers, or lipid bilayers. These provide a means to seal-in and retain cargo and to direct MSNP interactions with and internalization by target cells. Application of MSNPs as nanocarriers requires biocompatibility and low toxicity. Here the intrinsic porosity of the MSNP surface reduces the extent of hydrogen bonding or electrostatic interactions with cell membranes as does surface coating with polymers or lipid bilayers. Furthermore, the high surface area and low extent of condensation of the MSNP siloxane framework promote a high rate of dissolution into soluble silicic acid species, which are found to be nontoxic. Potential toxicity is further mitigated by the high drug capacity of MSNPs, which greatly reduces needed dosages compared with other nanocarriers. We anticipate that future generations of MSNPs incorporating molecular machines and encapsulated by membrane-like lipid bilayers will achieve a new level of controlled cellular interactions.

  • codelivery of an optimal drug sirna combination using Mesoporous Silica Nanoparticles to overcome drug resistance in breast cancer in vitro and in vivo
    ACS Nano, 2013
    Co-Authors: Huan Meng, Jeffrey I Zink, Tian Xia, Haiyuan Zhang, Xiang Wang, Sijie Lin, Yang Zhao, Min Xue, Wilson X Mai, Andre E. Nel
    Abstract:

    We used a multifunctional Mesoporous Silica Nanoparticle (MSNP) carrier to overcome doxorubicin (Dox) resistance in a multidrug resistant (MDR) human breast cancer xenograft by codelivering Dox and siRNA that targets the P-glycoprotein (Pgp) drug exporter. The Pgp siRNA selection from among a series of drug resistance targets was achieved by performing high throughput screening in a MDR breast cancer cell line, MCF-7/MDR. Following the establishment of a MCF-7/MDR xenograft model in nude mice, we demonstrated that a 50 nm MSNP, functionalized by a polyethyleneimine–polyethylene glycol (PEI-PEG) copolymer, provides protected delivery of stably bound Dox and Pgp siRNA to the tumor site. The effective biodistribution and reduced reticuloendothelial uptake, as a result of our nanocarrier design, allowed us to achieve an 8% enhanced permeability and retention effect at the tumor site. Compared to free Dox or the carrier loaded with either drug or siRNA alone, the dual delivery system resulted in synergistic in...

Victor S.-y. Lin - One of the best experts on this subject based on the ideXlab platform.

  • gold functionalized Mesoporous Silica Nanoparticle mediated protein and dna codelivery to plant cells via the biolistic method
    Advanced Functional Materials, 2012
    Co-Authors: Susana Martinortigosa, Victor S.-y. Lin, Brian G Trewyn, Justin S Valenstein, Kan Wang
    Abstract:

    The synthesis and characterization of a gold Nanoparticle functionalized Mesoporous Silica Nanoparticle (Au-MSN) platform for codelivery of proteins and plasmid DNA to plant tissues using a biolistic particle delivery system is reported. The in vitro uptake and release profiles of fluorescently labeled bovine serum albumin (BSA) and enhanced green fluorescent protein (eGFP) are investigated. As a proof-of-concept demonstration, Au-MSN with large average pore diameters (10 nm) are shown to deliver and subsequently release proteins and plasmid DNA to the same cell after passing through the plant cell wall upon bombardment. Release of fluorescent eGFP indicates the delivery of active, non-denatured proteins to plant cells. This advance represents the first example of biolistic-mediated codelivery of proteins and plasmid DNA to plant cells via gold-functionalized MSN and provides a powerful tool for both fundamental and applied research of plant sciences.

  • ligand conformation dictates membrane and endosomal trafficking of arginine glycine aspartate rgd functionalized Mesoporous Silica Nanoparticles
    Chemistry: A European Journal, 2012
    Co-Authors: Iju Fang, Victor S.-y. Lin, Igor I. Slowing, Brian G Trewyn
    Abstract:

    Recent breakthrough research on Mesoporous Silica Nanoparticle (MSN) materials has illustrated their significant potential in biological applications due to their excellent drug delivery and endocytotic behavior. We set out to determine if MSN, covalently functionalized with conformation specific bioactive molecules (either linear or cyclic RGD ligands), behave towards mammalian cells in a similar manner as the free ligands. We discovered that RGD immobilized on the MSN surface did not influence the integrity of the porous matrix and improved the endocytosis efficiency of the MSN materials. Through competition experiments with free RGD ligands, we also discovered a conformation specific receptor–integrin association. The interaction between RGD immobilized on the MSN surface and integrins plays an important role in endosome trafficking, specifically dictating the kinetics of endosomal escape. Thus, covalent functionalization of biomolecules on MSN assists in the design of a system for controlling the interface with cancer cells.

  • luciferase and luciferin co immobilized Mesoporous Silica Nanoparticle materials for intracellular biocatalysis
    Journal of the American Chemical Society, 2011
    Co-Authors: Xiaoxing Sun, Victor S.-y. Lin, Igor I. Slowing, Yannan Zhao, Brian G Trewyn
    Abstract:

    We report a gold Nanoparticle (AuNP)-capped Mesoporous Silica Nanoparticle (Au-MSN) platform for intracellular codelivery of an enzyme and a substrate with retention of bioactivity. As a proof-of-concept demonstration, Au-MSNs are shown to release luciferin from the interior pores of MSN upon AuNP uncapping in response to disulfide-reducing antioxidants and codeliver bioactive luciferase from the PEGylated exterior surface of Au-MSN to Hela cells. The effectiveness of luciferase-catalyzed luciferin oxidation and luminescence emission in the presence of intracellular ATP was measured by a luminometer. Overall, the chemical tailorability of the Au-MSN platform to retain enzyme bioactivity, the ability to codeliver enzyme and substrate, and the potential for imaging tumor growth and metastasis afforded by intracellular ATP- and glutathione-dependent bioluminescence make this platform appealing for intracellular controlled catalysis and tumor imaging.

  • Functionalized Mesoporous Silica Nanoparticle-based visible light responsive controlled release delivery system.
    Chemical communications (Cambridge England), 2011
    Co-Authors: Nikola Ž. Knežević, Brian G Trewyn, Victor S.-y. Lin
    Abstract:

    A supramolecular assembly for visible light responsive release of cargo molecules is presented. Sulforhodamine 101 was loaded inside the mesopores of mercaptopropyl-functionalized Mesoporous Silica Nanoparticles (MP-MSN) and entrapped by mercaptopropyl-coordinated Ru(bpy)2(PPh3)-moieties. Irradiation with visible light triggers the release of capping species and loaded molecules.

  • capped Mesoporous Silica Nanoparticles as stimuli responsive controlled release systems for intracellular drug gene delivery
    Expert Opinion on Drug Delivery, 2010
    Co-Authors: Yannan Zhao, Igor I. Slowing, Brian G Trewyn, Juan L Viveroescoto, Victor S.-y. Lin
    Abstract:

    Importance of the field: The incorporation of stimuli-responsive properties into nanostructured systems has recently attracted significant attention in the research of intracellular drug/gene delivery. In particular, numerous surface-functionalized, end-capped Mesoporous Silica Nanoparticle (MSN) materials have been designed as efficient stimuli-responsive controlled release systems with the advantageous ‘zero premature release’ property.Areas covered in this review: Herein, the most recent research progress on the design of biocompatible, capped MSN materials for stimuli-responsive intracellular controlled release of therapeutics and genes is reviewed. A series of hard and soft caps for drug encapsulation and a variety of internal and external stimuli for controlled release of different cargoes are summarized. Recent investigations on the biocompatibility of MSN both in vitro and in vivo are also discussed.What the reader will gain: The reader will gain an understanding of the challenges for the future e...

Igor I. Slowing - One of the best experts on this subject based on the ideXlab platform.

  • probing surface hydrogen bonding and dynamics by natural abundance multidimensional 17o dnp nmr spectroscopy
    Journal of Physical Chemistry C, 2016
    Co-Authors: Frederic A Perras, Igor I. Slowing, Umesh Chaudhary, Marek Pruski
    Abstract:

    Dynamic nuclear polarization (DNP)-enhanced solid-state nuclear magnetic resonance (SSNMR) spectroscopy is increasingly being used as a tool for the atomic-level characterization of surface sites. DNP surface-enhanced SSNMR spectroscopy of materials has, however, been limited to studying relatively receptive nuclei, and the particularly rare 17O nuclide, which is of great interest for materials science, has not been utilized. We demonstrate that advanced 17O SSNMR experiments can be performed on surface species at natural isotopic abundance using DNP. We use 17O DNP surface-enhanced 2D SSNMR to measure 17O{1H} HETCOR spectra as well as dipolar oscillations on a series of thermally treated Mesoporous Silica Nanoparticle samples having different pore diameters. These experiments allow for a nonintrusive and unambiguous characterization of hydrogen bonding and dynamics at the surface of the material; no other single experiment can give such details about the interactions at the surface. Our data show that, u...

  • silanol assisted carbinolamine formation in an amine functionalized Mesoporous Silica surface theoretical investigation by fragmentation methods
    Journal of Physical Chemistry B, 2016
    Co-Authors: Ana Paula De Lima Batista, Igor I. Slowing, Federico Zahariev, Ataualpa A C Braga, Fernando R Ornellas, Mark S Gordon
    Abstract:

    The aldol reaction catalyzed by an amine-substituted Mesoporous Silica Nanoparticle (amine-MSN) surface was investigated using a large molecular cluster model (Si392O958C6NH361) combined with the surface integrated molecular orbital/molecular mechanics (SIMOMM) and fragment molecular orbital (FMO) methods. Three distinct pathways for the carbinolamine formation, the first step of the amine-catalyzed aldol reaction, are proposed and investigated in order to elucidate the role of the silanol environment on the catalytic capability of the amine-MSN material. The computational study reveals that the most likely mechanism involves the silanol groups actively participating in the reaction, forming and breaking covalent bonds in the carbinolamine step. Therefore, the active participation of MSN silanol groups in the reaction mechanism leads to a significant reduction in the overall energy barrier for the carbinolamine formation. In addition, a comparison between the findings using a minimal cluster model and the...

  • ligand conformation dictates membrane and endosomal trafficking of arginine glycine aspartate rgd functionalized Mesoporous Silica Nanoparticles
    Chemistry: A European Journal, 2012
    Co-Authors: Iju Fang, Victor S.-y. Lin, Igor I. Slowing, Brian G Trewyn
    Abstract:

    Recent breakthrough research on Mesoporous Silica Nanoparticle (MSN) materials has illustrated their significant potential in biological applications due to their excellent drug delivery and endocytotic behavior. We set out to determine if MSN, covalently functionalized with conformation specific bioactive molecules (either linear or cyclic RGD ligands), behave towards mammalian cells in a similar manner as the free ligands. We discovered that RGD immobilized on the MSN surface did not influence the integrity of the porous matrix and improved the endocytosis efficiency of the MSN materials. Through competition experiments with free RGD ligands, we also discovered a conformation specific receptor–integrin association. The interaction between RGD immobilized on the MSN surface and integrins plays an important role in endosome trafficking, specifically dictating the kinetics of endosomal escape. Thus, covalent functionalization of biomolecules on MSN assists in the design of a system for controlling the interface with cancer cells.

  • luciferase and luciferin co immobilized Mesoporous Silica Nanoparticle materials for intracellular biocatalysis
    Journal of the American Chemical Society, 2011
    Co-Authors: Xiaoxing Sun, Victor S.-y. Lin, Igor I. Slowing, Yannan Zhao, Brian G Trewyn
    Abstract:

    We report a gold Nanoparticle (AuNP)-capped Mesoporous Silica Nanoparticle (Au-MSN) platform for intracellular codelivery of an enzyme and a substrate with retention of bioactivity. As a proof-of-concept demonstration, Au-MSNs are shown to release luciferin from the interior pores of MSN upon AuNP uncapping in response to disulfide-reducing antioxidants and codeliver bioactive luciferase from the PEGylated exterior surface of Au-MSN to Hela cells. The effectiveness of luciferase-catalyzed luciferin oxidation and luminescence emission in the presence of intracellular ATP was measured by a luminometer. Overall, the chemical tailorability of the Au-MSN platform to retain enzyme bioactivity, the ability to codeliver enzyme and substrate, and the potential for imaging tumor growth and metastasis afforded by intracellular ATP- and glutathione-dependent bioluminescence make this platform appealing for intracellular controlled catalysis and tumor imaging.

  • capped Mesoporous Silica Nanoparticles as stimuli responsive controlled release systems for intracellular drug gene delivery
    Expert Opinion on Drug Delivery, 2010
    Co-Authors: Yannan Zhao, Igor I. Slowing, Brian G Trewyn, Juan L Viveroescoto, Victor S.-y. Lin
    Abstract:

    Importance of the field: The incorporation of stimuli-responsive properties into nanostructured systems has recently attracted significant attention in the research of intracellular drug/gene delivery. In particular, numerous surface-functionalized, end-capped Mesoporous Silica Nanoparticle (MSN) materials have been designed as efficient stimuli-responsive controlled release systems with the advantageous ‘zero premature release’ property.Areas covered in this review: Herein, the most recent research progress on the design of biocompatible, capped MSN materials for stimuli-responsive intracellular controlled release of therapeutics and genes is reviewed. A series of hard and soft caps for drug encapsulation and a variety of internal and external stimuli for controlled release of different cargoes are summarized. Recent investigations on the biocompatibility of MSN both in vitro and in vivo are also discussed.What the reader will gain: The reader will gain an understanding of the challenges for the future e...