Surface Of Mesoporous Silica Nanoparticles Research Articles

Imprinting the location of an in-built RAFT agent and selective grafting of polymer chains inside or outside the pores of mesoporous silica nanoparticles

Abstract Mesoporous silica nanoparticles (MSNs) primed with RAFT agent were synthesized via co-condensation of tetraethoxysilane (TEOS) and organoalkoxysilane based RAFT agent. The nature of the R group in organoalkoxysilane based RAFT agent was varied in order to control the preferential location of polymer grafting. Two different RAFT agents were prepared, one RAFT agent contained phenyl ethyl as R group, and other RAFT agent contained isobutyric acid as R group. The stability of the organoalkoxysilane based RAFT agents was confirmed employing UV–Visible spectroscopy and 1H solution NMR spectroscopy techniques. Succeeding this RAFT functionalized MSNs preparation, surface-initiated RAFT polymerization was carried out using N-isopropylacrylamide (NIPAM). RAFT and polymer functionalized MSNs were then characterized by diverse techniques such as FT-IR, TGA, UV–Visible spectroscopy, surface area measurement, X-ray photoelectron spectroscopy (XPS), 13C and 29Si solid-state NMR spectroscopy. The outcome of utilizing different types of organoalkoxysilane based RAFT agent on the morphology was examined using SEM and TEM. Spherical and cuboid shape was observed in the case of RAFT–COOH–MSNs and RAFT-Ph-MSNs respectively. Higher percentage of polymer grafting was observed in case of PNIPAM–COOH–MSNs in comparison to PNIPAM-Ph-MSNs. The realization of preferential grafting of polymer on exterior or interior surface of RAFT MSNs was established using pore size/volume analysis by BET as well as by XPS. The characteristic resonances in 13C and 29Si solid-state NMR and characteristic vibrations in FT-IR, confirms successful synthesis of organic-inorganic hybrids. The analysis of thermoresponsiveness of PNIPAM grafted MSNs was experimented by drug loading and release studies at different temperatures as well as by confocal laser scanning microscopy.

Surface functionalization of mesoporous silica nanoparticles with pyronine derivative for selective detection of hydrogen sulfide in aqueous solution

The selective detection of hydrogen sulfide (H2S) in aqueous solution has drawn increasing attention over the past decade. Although many fluorescent chemosensors in homogeneous solutions have been developed, the creation of rapid, highly sensitive and selective fluorescent nanoparticle sensors for detection of H2S are still less reported. In the present work, a novel organic-inorganic composite fluorescent sensor, M-SiO2@PYR, was synthesized by covalent coupling pyronine (PYR) on the solid surface of mesoporous silica nanoparticles. The obtained mesoporous nanoparticles were characterized by TEM and BET measurements. The chemical immobilization of organic fluorophores on the silica nanoparticles were analyzed by FT-IR, XPS, TGA, and solid state NMR methods. The fluorescent mesoporous nanoparticle sensor, M-SiO2@PYR, was found to show sensitive and selective quenching responses toward H2S in aqueous solution compared to a series of competitive analytes. The nanoparticle sensor also displayed a low detection limit of 103.6 nM to H2S, illustrating a high sensitivity. Moreover, the detection of H2S could be also realized in biological fluids like serum or urine. The present work provides a novel way to prepare fluorescent sensor for detecting biothiols in aqueous solution, which may be further used to develop discriminative sensor for multiple biothiols by modulating surface modification.

Nanoapplication of a Resistance Inducer to Reduce Phytophthora Disease in Pineapple (Ananas comosus L.).

Treatment of plants with a variety of abiotic and biotic inducers causes induced resistance to pathogen attack. In this study, the effect of four resistance inducers on plant diseases caused by Phytophthora cinnamomi was screened in vivo initially by using lupin, a susceptible model plant. Lupin pretreated with 0.5 mM salicylic acid (SA) showed effective resistance against P. cinnamomi with restricted lesions. Then, mesoporous silica nanoparticles (MSNs) with particle size around 20 nm and approximate pore size of 3.0 nm were synthesized and functionalized for loading and importing SA to pineapple plantlets. Decanethiol gatekeepers were introduced to the surface of MSNs via glutathione (GSH)–cleavable disulfide linkages to cover the pore entrance, which was confirmed through using Raman spectroscopy. Through free diffusion, the loading efficiency of SA in MSNs gated with gatekeepers was 11.7%, but was lower in MSNs without gatekeepers (8.0%). In addition, in vitro release profile of SA from gatekeeper-capped MSNs indicated that higher concentrations of GSH resulted in more cargo release. Moreover, the experiments in planta showed that the application of MSNs as a resistance inducer delivery system significantly improved pineapple resistance to P. cinnamomi in terms of inhibiting lesion development and improving root growth of infected plants, compared to the use of free SA and MSNs without gatekeepers. The analysis of SA, GSH, and defense-related genes, of PR1 and PR5, further confirmed that the slow and prolonged release of SA from MSNs inside the roots of pineapple plants was achieved through a redox-stimuli release mechanism. Therefore, the application of MSNs with redox-responsive gatekeepers has shown great potential as an efficient tool for delivering chemicals into plants in a controllable way.

Destruction of tumor mass by gadolinium-loaded nanoparticles irradiated with monochromatic X-rays: Implications for the Auger therapy

Synchrotron generated monochromatic X-rays can be precisely tuned to the K-shell energy of high Z materials resulting in the release of the Auger electrons. In this work, we have employed this mechanism to destruct tumor spheroids. We first loaded gadolinium onto the surface of mesoporous silica nanoparticles (MSNs) producing gadolinium-loaded MSN (Gd-MSN). When Gd-MSN was added to the tumor spheroids, we observed efficient uptake and uniform distribution of Gd-MSN. Gd-MSN also can be taken up into cancer cells and localize to a site just outside of the cell nucleus. Exposure of the Gd-MSN containing tumor spheroids to monochromatic X-ray beams resulted in almost complete destruction. Importantly, this effect was observed at an energy level of 50.25 keV, but not with 50.0 keV. These results suggest that it is possible to use precisely tuned monochromatic X-rays to destruct tumor mass loaded with high Z materials, while sparing other cells. Our experiments point to the importance of nanoparticles to facilitate loading of gadolinium to tumor spheroids and to localize at a site close to the nucleus. Because the nanoparticles can target to tumor, our study opens up the possibility of developing a new type of radiation therapy for cancer.

Temperature-sensitive polypeptide brushes-coated mesoporous silica nanoparticles for dual-responsive drug release

A biopolymer-inorganic hybrid system (MSN@PBLGF) is designed and fabricated from mesoporous silica nanoparticles (MSNs) and folic acid (FA)-terminated temperature-sensitive synthetic polypeptide, i.e., poly(γ-benzyl-l-glutamate) (PBLG) derivative, through a thiol-disulfide exchange reaction, where MSNs with high drug loading capacity serve as drug nanocarriers and the biocompatible PBLG biopolymer brushes installed on MSN surface through disulfide bonds endow the system with tumor-specific recognition ability and GSH/temperature dual-stimuli responsiveness. Controlled drug release experiments indicate that DOX can be tightly hosted in the system with limited premature release, but efficiently released in response to an increased concentration of GSH and/or an elevated temperature. Intracellular experiments demonstrate that the DOX-loaded MSN@PBLGF nanohybrid shows outstanding cellular uptake and cell-growth inhibition effects on human lung cancer cell line A549 in comparison with healthy human cells such as hepatocyte cells LO2.

Thiolated polymer and Cell-Penetrating Peptide dual-surface functionalization of mesoporous silicon nanoparticles to overcome intestinal barriers

For orally administered nanocarriers, being efficiently absorbed by the epithelium and penetrating through the mucus that covers the epithelium are twin challengeable barriers on the way to make drugs work. However, mucus penetration and epithelial absorption require quite different surface properties that nanocarriers possess. Thereby, we designed a dual-surficial-functionalized mesoporous silica nanoparticles (MSN) with thiolation Polymer (PSH) and Cell-Penetrating Peptide (CPP), which promote the mucoadhesion and cellular interactions, respectively, to boost the intestinal permeability of MSN-CPP-PSH, for efficient delivery of oral drugs. As a result, MSN-CPP-PSH showed excellent penetration across the mucus layer and high epithelial absorption using a mucus-secreting epithelial cell model. After investigating the behavior and integrity of MSN-CPP-PSH in the process of mucus penetrating and epithelium uptaking, the PSH molecules were observed gradually dissociated from the surface of MSN as it penetrated across mucus, and the CPP-covering core was revealed in time for the subsequent transepithelial transport. Biodistribution studies demonstrated this newly thiolated-polymers had quite mucoadhesive strength and greatly increased the intestinal residence time. Finally, MSN-CPP-PSH exhibits 6.76-fold in the relative bioavailability of lopinavir (LNV), as compared to oral free LNV. Our study demonstrated this newly synthesized PSH can play as a dissociable “mucus-adherent” agent to facilitate mucoadhesion and mucopenetration of nanocarriers, and also provided a strategy to overcome the diffusion barrier of mucus and absorption barrier of epithelium simultaneously.

Assembly of Multicomponent Nano-Bioconjugates Composed of Mesoporous Silica Nanoparticles, Proteins, and Gold Nanoparticles.

The purpose of this work was the assembly of multicomponent nano-bioconjugates based on mesoporous silica nanoparticles (MSNs), proteins (bovine serum albumin, BSA, or lysozyme, LYZ), and gold nanoparticles (GNPs). These nano-bioconjugates may find applications in nanomedicine as theranostic devices. Indeed, MSNs can act as drug carriers, proteins stabilize MSNs within the bloodstream, or may have therapeutic or targeting functions. Finally, GNPs can either be used as contrast agents for imaging or for photothermal therapy. Here, amino-functionalized MSNs (MSN–NH2) were synthesized and characterized through various techniques (small angle X-rays scattering TEM, N2 adsorption/desorption isotherms, and thermogravimetric analysis (TGA)). BSA or lysozyme were then grafted on the external surface of MSN–NH2 to obtain MSN–BSA and MSN–LYZ bioconjugates, respectively. Protein immobilization on MSNs surface was confirmed by Fourier transform infrared spectroscopy, ζ-potential measurements, and TGA, which also allowed the estimation of protein loading. The MSN–protein samples were then dispersed in a GNP solution to obtain MSN–protein–GNPs nano-bioconjugates. Transmission electron microscopy (TEM) analysis showed the occurrence of GNPs on the MSN–protein surface, whereas almost no GNPs occurred in the protein-free control samples. Fluorescence and Raman spectroscopies suggested that proteins–GNP interactions involve tryptophan residues.

Hybrid mesoporous silica nanospheres modified by poly (NIPAM-co-AA) for drug delivery

The synthesis of drug delivery systems based on surface-modified mesoporous silica hollow structures remains a huge challenge. In this paper, we have obtained hollow mesoporous silica nanoparticles (MSNs) by surfactant directed sol-gel assisted hydrothermal treatment. The MSNs have the inorganic-organic hybrid frameworks with uniform diameter distribution (260 nm), and their specific surface area, mesoporous size and pore volume are 540 m2 g−1, 3.7 nm, 0.58 cm3 g−1, respectively. It was proved that the preparation of hollow ethane-bridged nanospheres with two silicon source was due to the high crosslinking of the silicone interface and hydrothermal treatment, providing a new approach for the study of drug-loaded and controlled release behavior. Based on the synthesis of MSNs, MSNs were modified by methacryloxy propyl trimethoxyl silane (MPS) on the surface of MSNs. Then N-isopropylacryamide (NIPAM) and acrylic acid (AA) were grafted onto the surface of modified MSNs. The hollow ethane-bridged PNA–MSNs (poly (NIPAM-co-acrylic acid)-MSNs) with two silicon source were prepared successfully. Due to their distinctive hollow structure, PNA–MSNs demonstrated high drug encapsulation efficiency (70.4% ± 2.9%). The experiment results proved that the modified hollow nanoparticles not only had good biocompatibility and stability, but also possessed pH-/thermal-dual responsiveness in drug release.

Efficient Photodynamic Therapy of Prostate Cancer Cells through an Improved Targeting of the Cation-Independent Mannose 6-Phosphate Receptor.

The aim of the present work is the development of highly efficient targeting molecules to specifically address mesoporous silica nanoparticles (MSNs) designed for the photodynamic therapy (PDT) of prostate cancer. We chose the strategy to develop a novel compound that allows the improvement of the targeting of the cation-independent mannose 6-phosphate receptor, which is overexpressed in prostate cancer. This original sugar, a dimannoside-carboxylate (M6C-Man) grafted on the surface of MSN for PDT applications, leads to a higher endocytosis and thus increases the efficacy of MSNs.

Co-responsive smart cyclodextrin-gated mesoporous silica nanoparticles with ligand-receptor engagement for anti-cancer treatment

Combination of both internal- and external-stimuli responsive strategies in nanoplatforms can maximize therapeutic outcomes by overcoming drug efflux-mediated resistance and prolonging sustained release of therapeutic payloads in controlled and sequential manner. Here, we show a light/redox dual-stimuli responsive β-cyclodextrin (β-CD)-gated mesoporous silica nanoparticles (MSN) that can effectively load and seal the chemotherapeutics, doxorubicin (DOX), inside MSN with a dual-capped system. The primary gatekeeper was achieved by capping β-CD via a disulfide linkage. An azobenzene/galactose-grafted polymer (GAP) was introduced to functionalize the MSN surface through host-guest interaction. GAP not only served as a secondary non-covalent polymer-gatekeeper to further prevent molecules from leaking out, but also presented targeting ligand for engagement of the asialoglycoprotein receptor (ASGPR) on hepatocellular carcinoma (HepG2) cells. The controlled and stimuli release of DOX could be realized via dissociation of azobenzene moieties from β-CD cage upon UV-irradiation, followed by liberation with the endogenous glutathione. The in vitro studies verified the redox-sensitive DOX release behavior, and the UV irradiation could accelerate this process to trigger DOX burst from MSN-ss-CD/GAP. Notably, the DOX@MSN-ss-CD/GAP could more efficiently deliver DOX into HepG2 cells and demonstrate enhanced cytotoxicity as compared with HeLa and COS7 cells. The smart MSN-ss-CD/GAP delivery system holds the potential for universal therapeutic uses in both biomedical research and clinical settings.

Loading zedoary oil into pH-sensitive chitosan grafted mesoporous silica nanoparticles via gate-penetration by supercritical CO2 (GPS)

Nanocarriers of the stimuli-responsive mesoporous silica nanoparticles (MSNs) have exhibited great potential on target-specific and controlled-release drug delivery. However, it is still a challenge to load drugs into this promising nanocarriers because of its gated structure. In this study, we developed a method named gate-penetration by supercritical CO2 (GPS) to successfully prepared zedoary oil loaded chitosan grafted MSNs (ZO@CS-MSNs). Quantitative analysis by high performance liquid chromatography demonstrated the composition ratio of six primary ingredients in zedoary oil remained constant after the drug loading process. Several process parameters of GPS were optimized, and the drug load of ZO reached 41.4 ± 1.2%. Morphology characterization by scanning electron microscope showed that ZO@CS-MSNs were spheres with diameter about 80 nm and a ‘gate’ structure was formed by chitosan on the surface of MSNs. Infrared and thermogravimetric analysis were performed to further confirm the structure of ZO@CS-MSNs. in vitro drug release test under different pH conditions indicated that ZO had a well pH-response release behavior, proving that ZO was transported into the inner channels of MSNs. The results state GPS is a promising way of high-efficacy and non-destructive to overcome the drug loading problems for stimuli-responsive MSN and further extend its application.

Codelivery of Plasmid and Curcumin with Mesoporous Silica Nanoparticles for Promoting Neurite Outgrowth.

Reactive oxygen species (ROS)-induced oxidative stress leads to neuron damage and is involved in the pathogenesis of chronic inflammation in neurodegenerative diseases (NDs), such as Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis. Researchers, therefore, are looking for antiinflammatory drugs and gene therapy approaches to slow down or even prevent neurological disorders. Combining therapeutics has shown a synergistic effect in the treatment of human diseases. Many nanocarriers could be designed for the simultaneous codelivery of drugs with genes to fight diseases. However, only a few researches have been performed in NDs. In this study, we developed a mesoporous silica nanoparticle (MSN)-based approach for neurodegenerative therapy. This MSN-based platform involved multiple designs in the targeted codelivery of (1) curcumin, a natural antioxidant product, to protect ROS-induced cell damage and (2) plasmid RhoG-DsRed, which is associated with the formation of lamellipodia and filopodia for promoting neurite outgrowth. At the same time, TAT peptide was introduced to the plasmid RhoG-DsRed via electrostatic interaction to elevate the efficiency of nonendocytic pathways and the nuclear plasmid delivery of RhoG-DsRed in cells for enhanced gene expression. Besides, such a plasmid RhoG-DsRed/TAT complex could work as a noncovalent gatekeeper. The release of curcumin inside the channel of the MSN could be triggered when the complex was dissociated from the MSN surface. Taken together, this MSN-based platform combining genetic and pharmacological manipulations of an actin cytoskeleton as well as oxidative stress provides an attractive way for ND therapy.

Biopebble Containers: DNA-Directed Surface Assembly of Mesoporous Silica Nanoparticles for Cell Studies.

The development of methods for colloidal self-assembly on solid surfaces is important for many applications in biomedical sciences. Toward this goal, described is a versatile class of mesoporous silica nanoparticles (MSN) that contain on their surface various types of DNA molecules to enable their self-assembly into micropatterned surface architectures useful for cell studies. Monodisperse dye-doped MSN are synthesized by biphase stratification and functionalized with an aptamer oligonucleotide that serves as gatekeeper for the triggered release of encapsulated molecular cargo, such as fluorescent dye rhodamine B or the anticancer drug doxorubicin. One or two additional types of oligonucleotides are installed on the MSN surface to enable DNA-directed immobilization on solid substrates bearing patterns of complementary capture oligonucleotides. It is demonstrated that this strategy can be used for efficient self-assembly of microstructured surface architectures, which not only promote the adhesion and guidance of cells but also are capable of affecting the fate of adhered cells through triggered release of their cargo. It is believed that this approach is useful for diverse applications in tissue engineering and nanobio sciences.

Cumulative directional calcium gluing between phosphate and silicate: A facile, robust and biocompatible strategy for siRNA delivery by amine-free non-positive vector

For siRNA therapeutics, the use of positively charged amine-rich delivery vectors has been indispensable, but the amine-associated toxicological responses remain a clinical conundrum. Herein, we report a new strategy of harnessing a biocompatible, biodegradable and well-tolerated nanomaterial as an amine-free non-positive carrier for siRNA delivery. By employing mesoporous silica nanoparticles (MSNs) as a biocompatible vector, siRNA is loaded nonconventionally through calcium ion (Ca2+)-mediated interconnection (calcium gluing) between phosphates of siRNA and surface silicates of MSNs in a sequential, cumulative and directional way. The “one-pot” gluing process utilizing endogenously abundant Ca2+ ions offers a simple but robust means of siRNA loading on the non-positive bare surface of MSNs without the aid of multi-amine functionalization, and thus minimizes the risk of amine-associated cytotoxicity and immunogenicity while keeping the intrinsic biocompatibility of MSNs. As demonstrated with loading of an anticancer siRNA, this strategy allows stable in vivo delivery of siRNA for targeted gene silencing, and capitalizes on the unique structural versatility of MSNs by simultaneously delivering a pore-loaded chemodrug to synergistically enhance the treatment efficacy. Therefore, the Ca2+-glued MSNs as a general siRNA carrier platform provide a less toxic, less laborious and more utilitarian delivery tool for more effective and safer siRNA therapeutics.

Enzyme-responsive mesoporous silica nanoparticles for tumor cells and mitochondria multistage-targeted drug delivery.

Background: Drug delivery systems (DDS) capable of targeting both cell and organelle levels are highly desirable for effective cancer therapy. In this study, we developed a novel enzyme-responsive, multistage-targeted anticancer DDS based on mesoporous silica nanoparticles (MSNs), which possessed both CD44-targeting and mitochondrial-targeting properties.Materials and methods: Triphenylphosphine (TPP), a mitochondria-targeting compound, was grafted onto the surface of MSNs firstly. Then, Doxorubicin (Dox) was encapsulated into the pore of MSNs, followed by capping with tumor-targeting molecules hyaluronic acid (HA) through electrostatic interactions to form the final product consist of Dox loaded, TPP attached, HA capped mesoporous silica nanoparticles (MSN-DPH).Results: Our results suggested that MSN-DPH was preferentially taken up by cancer cells via CD44 receptor-mediated endocytosis. Moreover, MSN-DPH mainly accumulated in mitochondria owing to the mitochondrial-targeting ability of TPP. Degradation of HA by overexpressed HAase facilitated the release of Dox in cancer cells. Thus, MSN-DPH efficiently killed the cancer cells while exhibited much lower cytotoxicity to normal cells.Conclusion: This study demonstrates a promising multistage-targeted DDS for cancer chemotherapy.

Super-pH-Sensitive Mesoporous Silica Nanoparticle-Based Drug Delivery System for Effective Combination Cancer Therapy.

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@MSN-ss-DTPP&DTCPP nanoparticles in tumor environment, in which DOX@MSN-ss-DTPP&DTCPP nanoparticles exhibited the preferred cytotoxicity toward αvβ3-positive human cervical carcinoma (HeLa) cells. We believe that the multifunctional dual-stimuli-sensitive MSN could provide an effective strategy for combinational tumor therapy.

Versatile Nanocarrier Based on Functionalized Mesoporous Silica Nanoparticles to Codeliver Osteogenic Gene and Drug for Enhanced Osteodifferentiation.

To achieve enhanced stimulatory effects on the osteogenic differentiation of stem cells, the combination of dual factors with synergistic bioactivity has been regarded as the most effective and powerful strategy. In this study, polylysine-modified polyethylenimine (PEI-PLL) copolymers with various molecular weight PEI blocks were first synthesized and evaluated focusing on their cytotoxicity and gene transfection efficiency, and the results demonstrated that the synthesized copolymer PEI-PLL-25k (synthesized using 25 kDa PEI) exhibited lower cytotoxicity and higher in vitro transfection efficiency than commercial PEI-25k (Mw = 25 kDa). In order to effectively load and deliver plasmid DNA and osteogenic drug dexamethasone (DEX), PEI-PLL-25k copolymer and arginine-glycine-aspartate (RGD) peptide were successively anchored onto the surface of mesoporous silica nanoparticles (MSNs) to construct the dual-factor delivery system, which allows the surface adsorption of DNA and DEX loading in the mesopores of MSNs. The modification of PEI-PLL-25k copolymer and RGD on nanoparticles was successfully characterized by various techniques. The functionalized MSNs with RGD conjugation on the surface showed good cytocompatibility as evidenced by in vitro cell viability assays and cytoskeleton observation. The dual-factor delivery system could quickly release plasmid DNA (pDNA), while releasing DEX in a sustained manner. When cultured with the vector bearing bone morphogenetic protein-2 (BMP-2) pDNA, the transfected bone mesenchymal stem cells (BMSCs) were capable of expressing BMP-2 protein. With the simultaneous delivery of DEX and the BMP-2 gene, this dual-factor delivery system could significantly enhance the level of osteogenic differentiation of BMSCs, as demonstrated by in vitro results of alkaline phosphatase (ALP) activity, expression of osteo-related genes, and calcium deposition. Therefore, the versatile functionalized MSNs nanocarrier for codelivery of osteogenic gene and drug may be considered as a promising dual-delivery system to synergistically enhance the osteogenic outcomes of stem cells.

Preparation and drug release application of pH and light dual-stimuli-responsive nanocarrier based on mesoporous silica nanoparticles

The spherical mesoporous silica nanoparticles (MSNs) with good dispersity and uniform pore structure were prepared and functionalized by amino and 2-bromoisobutyrate successively. The random copolymer brushes of 1′-(2-acryloxyethyl)-3′,3′-dimethyl-6-nitrospiro-(2H-1-benzopyran-2,2′-indoline) (SPMA) and methacrylic acid (MAA) on the surface of MSNs were obtained via chemical hydrolysis of the precursor random copolymer MSNs-g-P(SPMA-co-tert-butyl methacrylate (tBMA)) in acidic conditions. The pH or light stimuli-responsive behavior and the dual-responsive process were recorded by UV-Vis absorption spectroscopy and dynamic light scattering (DLS). Furthermore, doxorubicin (DOX) as model drug molecule was loaded into the polymer brushes (as the nanocarrier), and the controlled release processes of DOX under the external stimulations were studied to some extent.

Synthesis of Highly Ordered Mesoporous MCM-41: Selective External Functionalization by Time Control

Sol-gel synthesis is commonly used to modify the surface of mesoporous silica nanoparticles (MSN) with organic groups through the co-condensation method. The template removal, and the site-controlled addition of organic groups and their partial occlusion inside the framework walls are still a challenge in the one-pot synthesis. Here, we optimize the synthesis of amino-modified MSN by the combination of efficient template removal methodology with the precise time of the amino precursor addition to achieve superb mesoporous material. The addition after the growth process produces a sample with a significantly higher amount of NH2 on the external surface when compared to the standard procedure. The template removal by reflux with isopropanol/H+ eliminated ca. 90% of cetyltrimethylammonium bromide (CTAB), and preserved the mechanical and thermal properties, even with thin walls (2.1 nm). The synthesized nanoparticles possess stability, appropriate size, and a positive surface. This makes them excellent nanocarriers, especially in the biomedical field.

A dual-sensitive mesoporous silica nanoparticle based drug carrier for cancer synergetic therapy.

A multifunctional envelope-type mesoporous silica nanoparticle (MSN) was delicately designed for subcellular co-delivery of drug and therapeutic peptide to tumor cells. Firstly, a kind of cell apoptosis peptide (KLAKLAK)2 (KLA) was anchored on surface of MSN via disulfide bond to obtain MSN-SS-KLA. Subsequently, anticancer drug doxorubicin hydrochloride (DOX) was loaded into the pores of MSN-SS-KLA. Then, the drug loaded MSN-SS-KLA (DOX@MSN-SS-KLA) was further coated with bovine serum albumin (BSA) to obtain a biological media stable MSN based drug delivery system (DDS), DOX@MSN-SS-KLA/BSA, for cancer synergetic therapy. The results show that stability of the DOX@MSN-SS-KLA/BSA is much better than that of DOX@MSN-SS-KLA and it could keep well dispersed in serum for more than 24 h. After accumulating at tumor site by EPR effect, the DOX@MSN-SS-KLA/BSA could be effectively phagocytosed by HeLa cells and release apoptotic peptide KLA as well as DOX simultaneously responding to reductive stimulus inside the cells. In vitro cell experiment results show that the DOX@MSN-SS-KLA/BSA complex exhibits much better inhibition on HeLa cells compared with pure DOX, indicating that co-delivery of KLA and DOX is expected to achieve synergetic therapy of cancer.