Dendritic Mesoporous Silica Nanoparticles Research Articles

Dendritic Mesoporous Silica Nanoparticle Adjuvants Modified with Binuclear Aluminum Complex: Coordination Chemistry Dictates Adjuvanticity

AbstractAluminum‐containing adjuvants used in vaccine formulations suffer from low cellular immunity, severe aggregation, and accumulation in the brain. Conventional aluminosilicates widely used in the chemical industry focus mainly on acidic sites for catalytic applications, but they are rarely used as adjuvants. Reported here is an innovative “ligand‐assisted steric hindrance” strategy to create a high density of six‐coordinate VIAl−OH groups with basicity on dendritic mesoporous silica nanoparticles as new nanoadjuvants. Compared to four‐coordinate IVAl‐modified counterparts, VIAl−OH‐rich aluminosilicate nanoadjuvants enhance cellular delivery of antigens and provoke stronger cellular immunity. Moreover, the aluminum accumulation in the brain is more reduced than that with a commercial adjuvant. These results show that coordination chemistry can be used to control the adjuvanticity, providing new understanding in the development of next‐generation vaccine adjuvants.

Pt-confinement catalyst with dendritic hierarchical pores on excellent sulfur-resistance for hydrodesulfurization of dibenzothiophene and 4,6-dimethyldibenzothiophene

Metal confinement catalyst MoS2/Pt@TD-6%Ti (TD, TS-1/Dendritic mesoporous silica nanoparticles composite) in dendritic hierarchical pore structures was synthesized and showed excellent sulfur-resistance performance and stabilities in catalytic hydrodesulfurization reactions of probe sulfide molecules. The MoS2/Pt@TD-6%Ti catalyst combines the concepts of Pt-confinement effect and hydrogen spillover of Pt noble metal. The modified micropores of Mo/Pt@TD-6%Ti only allow the migration and dissociation of small H2 molecules (0.289 nm), and effectively keep the sulfur-containing compounds (e.g. H2S, 0.362 nm) outside. Thus, the MoS2/Pt@TD-6%Ti catalyst exhibits higher DBT and 4,6-DMDBT HDS activities because of the synergistic effect of the strong H2 dissociation ability of Pt and desulfurization ability of MoS2 with a lower catalyst cost. This new concept combining H2 dissociation performance of noble metal catalyst with the desulfurization ability of transition metal sulfide MoS2 can protect the noble metal catalyst avoiding deactivation and poison, and finally guarantee the higher activities for DBT and 4,6-DMDBT HDS.

Openwork@Dendritic Mesoporous Silica Nanoparticles for Lactate Depletion and Tumor Microenvironment Regulation

AbstractThe direct depletion of lactate accumulated in the tumor microenvironment holds promise for cancer therapy but remains challenging. Herein, we report a one‐pot synthesis of openwork@ dendritic mesoporous silica nanoparticles (ODMSNs) to address this problem. ODMSNs self‐assembled through a time‐resolved lamellar growth mechanism feature an openworked core and a dendritic shell, both constructed by silica nanosheets of ≈3 nm. With a large pore size, high surface area and pore volume, ODMSNs exhibited a high loading capacity (>0.7 g g−1) of lactate oxidase (LOX) and enabled intratumoral lactate depletion by >99.9 %, leading to anti‐angiogenesis, down‐regulation of vascular endothelial growth factor, and increased tumor hypoxia. The latter event facilitates the activation of a co‐delivered prodrug for enhancing anti‐tumor and anti‐metastasis efficacy. This study provides an innovative nano‐delivery system and demonstrates the first example of direct lactate‐depletion‐enabled chemotherapy.

Openwork@Dendritic Mesoporous Silica Nanoparticles for Lactate Depletion and Tumor Microenvironment Regulation.

The direct depletion of lactate accumulated in the tumor microenvironment holds promise for cancer therapy but remains challenging. Herein, we report a one-pot synthesis of openwork@ dendritic mesoporous silica nanoparticles (ODMSNs) to address this problem. ODMSNs self-assembled through a time-resolved lamellar growth mechanism feature an openworked core and a dendritic shell, both constructed by silica nanosheets of ≈3 nm. With a large pore size, high surface area and pore volume, ODMSNs exhibited a high loading capacity (>0.7 g g-1 ) of lactate oxidase (LOX) and enabled intratumoral lactate depletion by >99.9 %, leading to anti-angiogenesis, down-regulation of vascular endothelial growth factor, and increased tumor hypoxia. The latter event facilitates the activation of a co-delivered prodrug for enhancing anti-tumor and anti-metastasis efficacy. This study provides an innovative nano-delivery system and demonstrates the first example of direct lactate-depletion-enabled chemotherapy.

Poly(amino acid) Multilayers Modified Dendritic Mesoporous Silica Nanoparticles Achieve Effective Enzyme Stability for Ultrasensitive Immunoassay.

Enzyme-linked immunosorbent assay (ELISA) is one of the most common techniques in biomedical detection; however, the poor sensitivity in early diagnosis for some diseases seriously limits its application. In this work, we developed an ultrasensitive ELISA system that is based on horseradish peroxidase (HRP)-loaded dendritic mesoporous silica nanoparticles (DMSN) modified with poly(amino acid) multilayers (defined as DSHP). A large amount of HRP adsorption was achieved in center-radial mesoporous channels of DMSN because of the high specific surface area and large pore size, leading to significant signal amplification. Additionally, DSHP could not only effectively maintain HRP activity for at least 10 days but also provide preferable protection for HRP activity even at high temperatures or a wide pH range. Moreover, the DSHP system exhibited admirable signal amplification performance with a limit of detection of 0.667 fM and a wide detectable range from 6.67 × 10-4 to 6.67 × 105 pM, whose sensitivity was 104 times higher than that of the conventional ELISA. We believe that the DSHP will offer a new strategy for signal amplification of the ELISA system in clinical diagnosis.

The impact of ethanol and chlorobenzene in the structure regulation of dendritic mesoporous silica nanoparticles

The impact of ethanol and chlorobenzene in the structure regulation of dendritic mesoporous silica nanoparticles

Surface charge-controlled electron transfer and catalytic behavior of immobilized cytochrome P450 BM3 inside dendritic mesoporous silica nanoparticles.

Understanding the influencing factors on the reaction kinetics of P450 BM3 within confined spaces is essential for developing efficient P450 BM3 bioreactors. Herein, two dendritic mesoporous silica nanoparticles (OH-DMSNs and NH2-DMSNs) with similar pore size but opposite surface charge have been prepared and served as the vehicle to immobilize P450 BM3. With the help of the film-forming material of chitosan, P450 BM3/OH-DMSN and P450 BM3/NH2-DMSN composites were immobilized on GC electrode and characterized with electrochemical measurements. Compared with P450 BM3/OH-DMSNs/GCE, P450 BM3/NH2-DMSNs/GCE showed higher electron transfer efficiency with higher current charge and lower ks value. Besides, the generated catalytic current towards testosterone on P450 BM3/NH2-DMSNs/GCE was 1.81 times larger than P450 BM3/OH-DMSNs/GCE. Furthermore, P450 BM3 inside NH2-DMSNs displayed higher affinity towards testosterone with the lower Kmapp value of 244.82μM. These results are attributed to the positively charged internal walls of NH2-DMSNs so that P450 BM3 adapts to an orientation favorable for electron exchange with electrodes and substrate binding with the active sites. The present study provides fundamentals for regulating the surface charge to optimize redox process and catalytic behavior in CYP bioreactors through electrostatic interactions.

Glucose Oxidase Immobilization with Amino Dendritic Mesoporous Silica Nanoparticles and Its Application in Glucose Detection

Glucose Oxidase Immobilization with Amino Dendritic Mesoporous Silica Nanoparticles and Its Application in Glucose Detection

Dendritic Mesoporous Organosilica Nanoparticles: A pH-Triggered Autocatalytic Fenton Reaction System with Self-supplied H2O2 for Generation of High Levels of Reactive Oxygen Species.

Dendritic mesoporous silica nanoparticles represent a new biomedical application platform due to their special central radial pore structure for the loading of drugs and functional modification. Herein, we report functionalized dendritic mesoporous organosilica nanoparticles (DMONs), a pH-triggered Fenton reaction generator (TA/Fe@GOD@DMONs), incorporating natural glucose oxidase (GOD) in the DMONs with tannic acid (TA) grafted using Fe3+ on the surface, that have been designed and constructed for efficient tumor ablation with self-supplied H2O2 and accelerated conversion of Fe3+/Fe2+ by TA. In view of the deficiency of endogenous H2O2, the self-supply through the TA/Fe@GOD@DMONs platform represented a high-yielding source of peroxygen. Furthermore, the production of Fe2+ induced by TA greatly improved the efficiency of the Fenton reaction resulting in significant tumor inhibition. This new design represents as novel paradigm for the development of autocatalytic Fenton nanosystems for effective treatment of tumors.

Smart Protein-Based Formulation of Dendritic Mesoporous Silica Nanoparticles: Toward Oral Delivery of Insulin.

Oral insulin administration still represents a paramount quest that almost a century of continuous research attempts did not suffice to fulfill. Before pre‐clinical development, oral insulin products have first to be optimized in terms of encapsulation efficiency, protection against proteolysis, and intestinal permeation ability. With the use of dendritic mesoporous silica nanoparticles (DMSNs) as an insulin host and together with a protein‐based excipient, succinylated β‐lactoglobulin (BL), pH‐responsive tablets permitted the shielding of insulin from early release/degradation in the stomach and mediated insulin permeation across the intestinal cellular membrane. Following an original in vitro cellular assay based on insulin starvation, direct cellular fluorescent visualization has evidenced how DMSNs could ensure the intestinal cellular transport of insulin.

Design of Dendritic Large-Pore Mesoporous Silica Nanoparticles with Controlled Structure and Formation Mechanism in Dual-Templating Strategy.

Dendritic large-pore mesoporous silica nanoparticles (DLMSN) is an important biodegradable drug carrier due to its high porosity, which can be prepared by coassembly of a major template and an auxiliary template in aqueous solution, followed by hydrolysis of tetraethyl orthosilicate (TEOS). The auxiliary template is key to obtaining dendritic large-pore structures; however, how to choose the auxiliary template to obtain the desired pore structure is largely unknown. This is because the formation mechanism of DLMSN is still not clear. In this study, a series of therapeutic agent molecules were used as the auxiliary templates to study the control of the pore morphology of DLMSN. Transmission electron microscopy observation and theoretical modeling were used to study the micelle formation, and early stage silica formation was also observed. It is proposed that the silica branches and sheets formed by hydrolysis of TEOS on single micelle and micelle bundles, which formed the initial nanoparticles with spherical structures and new silica species growing on the early formed particles to form DLMSN. The fine control of pore morphology was demonstrated by using auxiliary templates with different structural characteristics, which were used for selective drug loading. This work provides a design strategy of how to choose suitable auxiliary templates for preparing DLMSN with desired pore structure for biomedical applications.

Chondroitin sulfate-functionalized 3D hierarchical flower-type mesoporous silica with a superior capacity for selective isolation of low density lipoprotein

Novel flower-type and three-dimensional porous nanoparticles are prepared for the isolation of low density lipoprotein (LDL). The amino-terminated dendritic mesoporous silica nanoparticles (A-DMSNs) show highly accessible central-radial pore (0.655 cm3 g−1) and surface area (362.263 m2 g−1), which play an important role in the superior adsorption capacity of 816.7 μg mg−1. The A-DMSNs is anchored with chondroitin sulfate (CS), shortly termed as ADC, for ensuring the selectivity of the adsorption. The adsorbed LDL is thereafter readily recovered at pH 9.0 by using 4 mmol L−1 Britton-Robinson buffer as stripping reagent, providing a recovery of 79.1%. ADC nanoparticles are further applied as sorbent for the selective isolation of LDL from simulated serum of hypercholesterolemia patient. High-purity LDL is achieved as demonstrated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) assays.

Hierarchical integration of degradable mesoporous silica nanoreservoirs and supramolecular dendrimer complex as a general-purpose tumor-targeted biomimetic nanoplatform for gene/small-molecule anticancer drug co-delivery.

Biomacromolecule therapeutic systems are intrinsically susceptible to degradation and denaturation. Nanoformulations are promising delivery vehicles for therapeutic biomacromolecules (antibodies, genes and so on). However, their applications in these areas still face many challenges including in vivo stability, premature leakage and accurate tumor recognition. In this study, a generally applicable new strategy for tumor-targeted delivery of biomacromolecules was developed through the hierarchical integration of degradable large-pore dendritic mesoporous silica nanoparticles (dMSNs) and cyclodextrin-modified polyamidoamine (PAMAM-CD) dendrimers. The orifice rim of the dMSNs was modified with ROS-responsive nitrophenyl-benzyl-carbonate (NBC) groups while disulfide-bonded azido ligands were subsequently grafted onto the inner channel walls via heterogeneous functionalization. The PAMAM-CD was then interred into the dendritic pores via click reactions and supramolecularly loaded with archetypal hydrophobic small-molecule anticancer model drug (SN-38) and therapeutic model gene (Bcl-2 siRNA), after which dMSNs were eventually coated with a 4T1 cancer cell membrane (CCM). Experimental evidence demonstrated that the synthesized nanocarriers could efficiently deliver therapeutic cargos to target cancer cells and release them in the tumor cytosol in a cascade-responsive manner. This biomimetic nanoplatform presents a novel strategy to efficiently deliver biomolecular therapeutics in a tumor-targeted manner.

Targeted Therapeutic-Immunomodulatory Nanoplatform Based on Noncrystalline Selenium.

Developing versatile nanomaterials has offered a myriad of opportunities to surmount cancer. In particular, the combination of therapy and immunomodulatory effect to further enhance immune response provides a new idea for effective tumor treatment. Herein, for the first time, an in situ growth strategy is developed to construct highly dispersed noncrystalline selenium nanoparticles (Se NPs) with thiolated cyclo(Arg-Gly-Asp-Phe-Lys-(mpa)) (RGD) peptide modification (R-Se@DMSND) for targeted cancer treatment. Se NPs could be homogeneously grown into the pore channels of dendritic mesoporous silica nanoparticles (DMSNs) since the DMSNs could stabilize Se NPs to prevent their aggregations. Moreover, Se NPs could not only act as a therapeutic agent, inducing ROS overproduction, to effectively suppress primary tumor but also as an immunomodulatory agent to simultaneously inhibit the growth of secondary tumors by enhancement of the immune response, as confirmed by the in vivo results. Such the therapeutic-immunomodulatory strategy for tumorous therapy combining with immunomodulation using one simple nanoplatform may pave a new avenue in the biomedical field.

K-modified Sn-containing dendritic mesoporous silica nanoparticles with tunable size and SnOx-silica interaction for the dehydrogenation of propane to propylene

Sn-containing dendritic mesoporous silica nanoparticles (Sn-DMSNs) were successfully prepared by the in-situ co-assembly method. Sn-DMSNs preserve original structural characteristics with three-dimensional and center-radial pore structure. The nanoparticle sizes of Sn-DMSNs can be controlled systematically from 170 nm to 360 nm depending on the molar ratio of NaSal/CTAB. Sn species are incorporated into the matrix of silica and the highly dispersed SnOx species are achieved. Sn-DMSNs catalysts exhibit excellent catalytic performance and stability in the propane dehydrogenation. The highly dispersed SnOx species rather than polymeric SnOx or crystalline SnO2 species contribute to the activation of propane and formation of propylene. The molar ratio of NaSal/CTAB also shows an important role in the structure of support and SnOx species. The excellent stability of Sn-DMSNs catalysts can be ascribed to the good ability to restrain coke formation and strong interaction between SnOx species and silica. The effect of potassium on Sn-DMSNs catalyst is also investigated.

Preparation of a hydrophilic interaction liquid chromatography material by sequential electrostatic deposition of layers of polyethyleneimine and hyaluronic acid for enrichment of glycopeptides.

A hydrophilic interaction liquid chromatography (HILIC) material with application in glycoproteomics was obtained by sequential deposition of polyethyleneimine (PEI) and hyaluronic acid (HA) on a negatively charged substrate by means of electrostatic self-assembly. This kind of surface modification endows the material with excellent hydrophilicity and warrants efficient glycopeptides enrichment. The feasibility of this enrichment was verified by using dendritic mesoporous silica nanoparticles (DMSNs) and magnetic graphene oxide (MagG) as negatively charged substrates for PEI and HA adhesion. The two final products (DMSNs@PEI@HA and MagG@PEI@HA) exhibit high enrichment selectivity (molar ratios of IgG and BSA digests = 1:500 and 1:1000), sensitivity (detection limit, 2 fmol/μL), recovery (>90%) and enrichment capacity (300mg/g). When using DMSNs@PEI@HA, 419N-glycopeptides derived from 105 glycoproteins were identified. When using MagG@PEI@HA, 376N-glycopeptides derived from 102 glycoproteins were identified, both from a 2μL serum sample. This is better than by methods described in previous reports. Graphical abstract Schematic representation of hydrophilic modification of negatively charged nanomaterial substrates by electrostatic self-assembly techniques to obtain hydrophilic interaction liquid chromatography (HILIC) materials for enrichment of N-glycopeptides.

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

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

Promoting Oxidative Stress in Cancer Starvation Therapy by Site-Specific Startup of Hyaluronic Acid-Enveloped Dual-Catalytic Nanoreactors.

Cutting off the glucose supply by glucose oxidase (GOx) has been regarded as an emerging strategy in cancer starvation therapy. However, the standalone GOx delivery suffered suboptimal potency for tumor elimination and potential risks of damaging vasculatures and normal organs during transportation. To enhance therapeutic efficacy and tumor specificity, a site-specific activated dual-catalytic nanoreactor was herein constructed by embedding GOx and ferrocene in hyaluronic acid (HA)-enveloped dendritic mesoporous silica nanoparticles to promote intratumoral oxidative stress in cancer starvation. In this nanoreactor, the encapsulated GOx served as the primary catalyst that accelerated oxidation of glucose and generation of H2O2, while the covalently linked ferrocene worked as the secondary catalyst for converting the upstream H2O2 to more toxic hydroxyl radicals (•OH) via a classic Fenton reaction. The outmost HA shell not only offered a shielding layer for preventing blood glucose from oxidation during nanoreactor transportation, thus minimizing the probable oxidative damage to normal tissues, but also imparted the nanoreactor with targeting ability for facilitating its internalization into CD44-overexpressing tumor cells. After the nanoreactor was endocytosed by target cells, the HA shell underwent hyaluronidase-triggered degradation in lysosomes and switched on the cascade catalytic reaction mediated by GOx and ferrocene. The resulting glucose exhaustion and •OH accumulation would effectively kill cancer cells and suppress tumor growth via combination of starvation and oxidative stress enhancement. Both in vitro and in vivo results indicated the significantly amplified therapeutic effects of this synergistic therapeutic strategy based on the dual-catalytic nanoreactor. Our study provides a new avenue for engineering therapeutic nanoreactors that take effect in a tumor-specific and orchestrated fashion for cancer starvation therapy.

Vanadium-containing dendritic mesoporous silica nanoparticles: Multifunctional catalysts for the oxidative and non-oxidative dehydrogenation of propane to propylene

Abstract Vanadium-containing dendritic mesoporous silica nanoparticles (V-DMSNs) were successfully synthesized by the co-assembly and anion-assisted method. The V-DMSNs were applied as catalysts for the oxidative dehydrogenation of propane and non-oxidative dehydrogenation of propane reactions. DMSNs support exhibits good hydrothermal stability according to the effect of ageing temperature and time on the structure. V-DMSNs with different vanadium contents preserve original structural characteristics of DMSNs support with three-dimensional and center-radial pore structure. The direct co-assembly process contributes to enhancing the interaction between the VO4 species and DMSNs support. A high concentration of highly dispersed and isolated VO4 species can be achieved on the present V-DMSNs systems. The V-DMSNs catalysts show better catalytic performance in the oxidative dehydrogenation of propane compared with corresponding V/DMSNs catalysts prepared by impregnation method. V-DMSNs catalysts also show the direct dehydrogenation ability and high stability. The appropriate concentrations of isolated and neighboring VOx species are favorably involved in propane activation and propylene formation. To further investigate the structural characteristics of catalysts dynamically responding to reactive conditions, the structures of active sites and deposited carbonaceous species were analyzed by in-situ Raman spectroscopy. This work gives a novel multifunctional catalyst that shows superior catalytic performance in the oxidative and non-oxidative dehydrogenation of propane reactions.

Highly Thiolated Dendritic Mesoporous Silica Nanoparticles with High-Content Gold as Nanozymes: The Nano-Gold Size Matters.

Thiolated dendritic mesoporous silica nanoparticles (T-DMSNs) with ultrahigh density of thiol groups (284.6 ± 9 μmol g-1) are synthesized and used to load gold nanoparticles with tunable sizes (1.2-2.7 nm) and high content (34.0 wt %). It is demonstrated that the size of gold nanoparticles has a significant impact on their peroxidase-mimicking activity. At an optimized size of 1.9 nm, T-DMSNs@Au exhibits the highest activity. Our contribution provides new insights into the rational design of nanozymes for future applications.