Colloidal Mesoporous Silica Nanoparticles Research Articles

A bioactive nanocomposite integrated specific TAMs target and synergistic TAMs repolarization for effective cancer immunotherapy

Reactive oxygen species (ROS) generated from photosensitizers exhibit great potential for repolarizing immunosuppressive tumor-associated macrophages (TAMs) toward the anti-tumor M1 phenotype, representing a promising cancer immunotherapy strategy. Nevertheless, their effectiveness in eliminating solid tumors is generally limited by the instability and inadequate TAMs-specific targeting of photosensitizers. Here, a novel core-shell integrated nano platform is proposed to achieve a coordinated strategy of repolarizing TAMs for potentiating cancer immunotherapy. Colloidal mesoporous silica nanoparticles (CMSN) are fabricated to encapsulate photosensitizer-Indocyanine Green (ICG) to improve their stability. Then ginseng-derived exosome (GsE) was coated on the surface of ICG/CMSN for targeting TAMs, as well as repolarizing TAMs concurrently, named ICG/CMSN@GsE. As expected, with the synergism of ICG and GsE, ICG/CMSN@GsE exhibited better stability, mild generation of ROS, favorable specificity toward M2-like macrophages, enhancing drug retention in tumors and superior TAMs repolarization potency, then exerted a potent antitumor effect. In vivo, experiment results also confirm the synergistic suppression of tumor growth accompanied by the increased presence of anti-tumor M1-like macrophages and maximal tumor damage. Taken together, by integrating the superiorities of TAMs targeting specificity and synergistic TAMs repolarization effect into a single nanoplatform, ICG/CMSN@GsE can readily serve as a safe and high-performance nanoplatform for enhanced cancer immunotherapy.

Oral spatial-to-point cascade targeting “sugar-coated bullets” for precise and safe chemotherapy by intervention Warburg effect

Glycolysis plays a vital role in the development and progression of tumors. Inhibiting glycolysis via smart and safe methods serves as a promising target for cancer therapy. Here, an oral “sugar-coated bullet” aiming at intervening Warburg effect is designed by coating colloidal mesoporous silica nanoparticles (CMS) encapsulating glycolysis inhibitor shikonin (SHK) with dextran, namely DCMS/SHK. The solubility and drug-loading capacity of SHK were enhanced by the special structure of CMS. Besides, the tempting bullets possess the spatial-to-point cascade targeting ability in delivering SHK from the colonic lumen to colon cancer cells and finally to PKM2. After DCMS/SHK reaches the colon, the dextran is hydrolyzed by dextranase especially existing in the colon site to glucose and the carriers become glucose-coated nanoparticles. The glucose-cloak nanoparticles would be largely endocytosed by tumor cells and complete the efficient delivery of SHK. The encapsulated SHK can prevent the glycolysis of cancer cells and thus inhibit tumor growth effectively. This work presents an ingenious cascade colon-targeting strategy to treat colon cancer by destroying cell energy metabolism.

Mesoporous Silica Nanoparticles with Dispersibility in Organic Solvents and Their Versatile Surface Modification.

Recently, colloidal mesoporous silica nanoparticles (MSNs) have attracted keen interest in scientific and technological fields. A significant issue regarding the effective use of colloidal MSNs is their dispersibility in various solvents, which is essential for their applications through surface modification. However, the dispersion media for colloidal MSNs have been extremely limited. Here, we report a new method for obtaining stable colloidal MSNs dispersed in various organic solvents through a gradual solvent exchange of colloidal MSNs from acidic water to an organic solvent by dialysis. This allows the colloidal MSNs to be dispersed as primary nanoparticles in organic solvents such as 1-butanol, 1-dodecanol, and tetrahydrofuran (THF), which are capable of hydrogen bonding with surface silanol groups. In addition, MSNs dispersed in THF can be modified with chlorosilanes while maintaining colloidal stability. Various organosilyl groups, such as trimethylsilyl and dimethylsilyl groups, can be densely grafted on the surfaces of MSNs. After trimethylsilylation, MSNs become dispersible even in a nonpolar and hydrophobic solvent like octane through the solvent exchange due to the preferential evaporation of THF. This method will offer a versatile approach to functionalizing colloidal MSNs toward a wide range of applications.

Redox/pH dual stimuli-responsive ZnO QDs-gated mesoporous silica nanoparticles as carriers in cancer therapy.

New drug delivery system (ZnO@CMS) of the redox and pH dual-stimuli responsive based on colloidal mesoporous silica nanoparticles (CMS) has been designed, in which zinc oxide quantum dots (ZnO QDs) as a capping agent was conjugated on the surface of nanoparticles by amide bonds. The release behaviour of doxorubicin (DOX) as the model drug from ZnO@CMS (ZnO@CMS-DOX) indicated the redox and pH dual-stimuli responsive properties due to the acidic dissolution of ZnO QDs and cleavage of the disulphide bonds. The haemolysis and bovine serum albumin adsorption assays showed that the modification of ZnO QDs on the mesoporous silica nanoparticles modified by mercapto groups (CMS-SH)(ZnO@CMS) had better biocompatibility compared to CMS-SH. The cell viability and cellular uptake tests revealed that the ZnO@CMS might achieve the antitumour effect on cancer cells due to the cytotoxicity of ZnO QDs. Therefore, ZnO@CMS might be potential nanocarriers of the drug delivery system in cancer therapy. The in vivo evaluation of ZnO@CMS would be carried out in future work.

Highly active enzymes immobilized in large pore colloidal mesoporous silica nanoparticles

Carbonic anhydrase and horseradish peroxidase are immobilized inside the ordered material by click reactions. Colorimetric assays prove their catalytic activity.

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

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

The effect on the morphology of mesoporous silica nanopaticles modified with different functional groups

Three types of nanomaterials marked were successfully synthesized by grafting HA, HOOC-PEG-COOH and NH2-ZnO QDs on the surface of colloidal mesoporous silica nanoparticles modified with sulfydryl, amino and carboxyl groups, respectively, which could be marked as FRET-CMS, CMS-PEG-COOH and ZnO-CMS, respectively. Moreover, the structural and particle properties of these nanomaterials were characterized by dynamic light scattering(DLS), ransmission electron microscopy (TEM) and nitrogen adsorption-desorption measurements. These nanoparticles presented with a relatively uniform spherical shape morphology with a diameter of about 100 nm. Furthermore, the mesoporous structure of the nanoparticles still remain but the pore diameter would decreased slightly after encapsulated with diffierent functional groups, which would be no obvious effect on the capacity for the drug loading and releasing. So these results indicated that the properties of CMS nanoparticles with different functional groups were worth researching for its application in drug delivery system in the future.

Synthesis and characterization of carboxyl modifiedmesoporous silica nanoparticles with disulfide bond as a cross linker

The purpose of this article is to prepare and characterize the disulfide bond and carboxyl-bifunctionalized colloidal mesoporous silica nanoparticles (CMS-SS-COOH). The CMS-SS-COOH was successfully synthesized by disulfide exchange and admiration methods. Moreover, the particle size and structural properties of CMS-SS-COOH were characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS) and fourier transform infrared spectroscopy (FT-IR).The results showed that the nanomaterials had a relatively uniform spherical morphology witha diameter of ca. 80 nm. This papermight provide a novel strategy to construct a stimulu-responsive drug delivery system in the future.

Synthesis and Characterization of Hyaluronic Acid Modified Colloidal Mesoporous Silica Nanoparticles

The colloidal mesoporous silica nanoparticles functionalized with hyaluronic acid (CMS-HA) were successfully synthesized by grafting hyaluronic acid onto the external surface of the amino-functionalized mesoporous silica nanoparticles (CMS-NH2). Moreover, the paticle properties of CMS-HA were characterized by fourier transform infrared spectroscopy (FT-IR), dynamic light scattering (DLS) and transmission electron microscopy (TEM). The nanomaterials were negatively charged and had a relatively uniform spherical morphology with about 100 nm in diameter, which could make it more compatible with blood. So the results suggested that the CMS-HA might be a critical nanomaterial for applying in target drug delivery system.

Colloidal Mesoporous Silica Nanoparticles as Strong Adhesives for Hydrogels and Biological Tissues.

Sub-100 nm colloidal mesoporous silica (CMS) nanoparticles are evaluated as an adhesive for hydrogels or biological tissues. Because the adhesion energy is proportional to the surface area of the nanoparticles, the CMS nanoparticles could provide a stronger adhesion between two hydrogels than the nonporous silica nanoparticles. In the case of 50 nm CMS nanoparticles with a pore diameter of 6.45 nm, the maximum adhesion energy was approximately 35.0 J/m2 at 3.0 wt %, whereas the 10 wt % nonporous silica nanoparticle solution showed only 7.0 J/m2. Moreover, the CMS nanoparticle solution had an adhesion energy of 22.0 J/m2 at 0.3 wt %, which was 11 times higher than that of the nonporous nanoparticles at the same concentration. Moreover, these CMS nanoparticles are demonstrated for adhering incised skin tissues of mouse, resulting in rapid healing even at a lower nanoparticle concentration. Finally, the CMS nanoparticles had added benefit of quick degradation in biological media because of their porous structure, which may prevent unwanted accumulation in tissues.

ChemInform Abstract: Colloidal Mesoporous Silica Nanoparticles

AbstractReview: 369 refs.

Doxorubicin-Functionalized Silica Nanoparticles Incorporated into a Thermoreversible Hydrogel and Intraperitoneally Administered Result in High Prostate Antitumor Activity and Reduced Cardiotoxicity of Doxorubicin.

Described here is an anticancer material based on colloidal mesoporous silica nanoparticles (MSNs) functionalized with doxorubicin (DOX), and incorporated into Pluronic F127 hydrogels for prolonged release, with a potential therapeutic application for prostate cancer treatment. The MSNs have spherical morphology, size of about 60 nm, surface area of 970 cm2 g-1 and average pore width of 2.0 nm. A high colloidal stability for the MSNs in the physiological medium used for in vivo administration (NaCl 0.9% w/v) could be attained in the presence of PF127 (from 5 to 18 wt %), where depletion repulsion forces prevent MSN agglomeration. By conjugating DOX, MSN and PF127 (18 wt %) in NaCl 0.9%, the hybrid system has a gelation temperature of 21 °C, which allowed its in vivo administration in the liquid form and further in situ gelation, generating a drug depot system inside the animals after peritoneal injection. The systems were tested in rats with chemically induced prostate cancer and, after this treatment, histopathological analyses confirmed (i) a reduction in the frequency of aggressive tumors; (ii) that the antitumor effect was dependent on MSN concentration; and most importantly (iii) the reduction of DOX intrinsic cardiotoxicity, indicating that the MSNs play a cardioprotective effect.

Colloidal mesoporous silica nanoparticles enhance the biological activity of resveratrol

The naturally occurring polyphenol resveratrol (RES) has attracted increasing attention in recent years due to its antioxidant, anti-inflammatory, and anticancer activity. However, resveratrol’s promising potential as a nutraceutical is hindered by its poor aqueous solubility, which limits its biological activity. Here we show that encapsulating resveratrol in colloidal mesoporous silica nanoparticles (MCM-48-RES) enhances its saturated solubility by ∼95% and increases its in vitro release kinetics compared to pure resveratrol. MCM-48-RES showed high loading capacity (20% w/w) and excellent encapsulation efficiency (100%). When tested against HT-29 and LS147T colon cancer cell lines, MCM-48-RES-mediated in vitro cell death was higher than that of pure resveratrol, mediated via the PARP and cIAP1 pathways. Finally, MCM-48-RES treatment also inhibited lipopolysaccharide-induced NF-κB activation in RAW264.7 cells, demonstrating improved anti-inflammatory activity. More broadly, our observations demonstrate the potential of colloidal mesoporous silica nanoparticles as next generation delivery carriers for hydrophobic nutraceuticals.

Photosensitizer doped colloidal mesoporous silica nanoparticles for three-photon photodynamic therapy

Multiphoton microscopy and nanoparticle-assisted photodynamic therapy are two important areas in biophotonics research. In this paper, we combined these two technologies together. Photosensitizer (HPPH) doped colloidal mesoporous silica nanoparticles were synthesized and systematically characterized. Based on a confocal microscope equipped with a 1560 nm femtosecond laser, we showed: (1) direct three-photon luminescence from HPPH doped nanoparticles, which were uptaken by tumor cells, and (2) cytotoxicity towards tumor cells by HPPH under three-photon excitation. Nanoparticle-assisted three-photon photodynamic therapy can be a promising technology for disease diagnosis and in vivo/clinical therapy.

Effective Use of Alkoxysilanes with Different Hydrolysis Rates for Particle Size Control of Aqueous Colloidal Mesostructured and Mesoporous Silica Nanoparticles by the Seed‐Growth Method

AbstractThe particle sizes of mesoporous silica nanoparticles most greatly affect their properties, including cellular uptake, cytotoxicity, and dispersity. The growth of colloidal mesostructured silica nanoparticles (CMSS) with particle sizes less than 100 nm was controlled by a modified seed‐growth method by using alkoxysilanes (Si(OR)4, R: Me, Et, Pr, and Bu) with different hydrolysis rates as additives. It was confirmed that the approximate matching of the hydrolysis rates of the added silanes with the consumption rates, determined by the total outer surface area of the seeds, is most important. CMSS with narrow particle‐size distributions (e.g., 60 or 80 nm in size) were successfully prepared. Si(OPr)4 was the most suitable additive, though Si(OEt)4 was also useful for controlled growth. Si(OBu)4 was usable but needed varied conditions for controlled growth. The mesostructures and the high dispersity of nanoparticles were retained, even after removal of the surfactants of the CMSS by dialysis. These findings should contribute to the more precise control of particle sizes of mesoporous silica nanoparticles and to the deeper understanding of their properties.

γ-PGA-coated mesoporous silica nanoparticles with covalently attached prodrugs for enhanced cellular uptake and intracellular GSH-responsive release.

Poor cellular uptake of drug delivery carriers and uncontrolled drug release remain to be the major obstacles in cancer therapy due to their low delivery efficiency. In this study, a multifunctional intracellular GSH (glutathione)-responsive silica-based drug delivery system with enhanced cellular uptake capability is developed. Uniform 50 nm colloidal mesoporous silica nanoparticles (MSNs) with mercaptopropyl-functionalized core and silanol-contained silica surface (MSNs-SHin ) are designed and fabricated as a platform for drug covalent attachment and particle surface modification. Doxorubicin (DOX) with primary amine group as an anticancer model drug is covalently conjugated to the mesopores of MSNs-SHin via disulfide bonds in the presence of a heterobifunctional linker (N-Succinimidyl 3-(2-pyridyldithio) propionate). Poly(γ-glutamic acid) (γ-PGA) can be coated onto the particle surface by sequential electrostatic adsorption of polyethyleneimine (PEI) and γ-PGA. The constructed delivery system exhibits enhanced cellular uptake via a speculated γ-glutamyl transpeptidase (GGT)-mediated endocytosis pathway and controlled drug release capacity via intracellular GSH-responsive disulfide-bond cleavage, and thus significantly inhibits the growth of cancer cells. The multifunctional delivery system paves a new way for developing high-efficient particle-based nanotherapeutic approach for cancer treatment.

A multifunctional role of trialkylbenzenes for the preparation of aqueous colloidal mesostructured/mesoporous silica nanoparticles with controlled pore size, particle diameter, and morphology.

Both the pore size and particle diameter of aqueous colloidal mesostructured/mesoporous silica nanoparticles (CMSS/CMPS) derived from tetrapropoxysilane were effectively and easily controlled by the addition of trialkylbenzenes (TAB). Aqueous highly dispersed CMPS with large pores were successfully obtained through removal of surfactants and TAB by a dialysis process. The pore size (from 4 nm to 8 nm) and particle diameter (from 50 nm to 380 nm) were more effectively enlarged by the addition of 1,3,5-triisopropylbenzene (TIPB) than 1,3,5-trimethylbenzene (TMB), and the enlargement did not cause the variation of the mesostructure and particle morphology. The larger molecular size and higher hydrophobicity of TIPB than TMB induce the incorporation of TIPB into micelles without the structural change. When TMB was used as TAB, the pore size of CMSS was also enlarged while the mesostructure and particle morphology were varied. Interestingly, when tetramethoxysilane and TIPB were used, CMSS with a very small particle diameter (20 nm) with concave surfaces and large mesopores were obtained, which may strongly be related to the initial nucleation of CMSS. A judicious choice of TAB and Si sources is quite important to control the mesostructure, size of mesopores, particle diameter, and morphology.

Preparation of Size-Controlled Monodisperse Colloidal Mesoporous Silica Nanoparticles and Fabrication of Colloidal Crystals

Although mesoporous silica particles are useful building blocks for colloidal crystals, mesoporous silica nanoparticles smaller than 100 nm with sufficient monodispersity and colloidal stability to enable thermodynamic assemblies have not been reported. Here, we report that highly monodisperse colloidal mesoporous silica nanoparticles (CMS) can be prepared by combining the preparation of colloidal mesoporous silica nanoparticles with a shortened nucleation time. The nanoparticles exhibited a uniform shape and relatively smooth surface because an undesirable aggregate dispersion process was avoided. In addition, the diameter of the nanoparticles was controlled by seed-growth without spontaneous nucleation, which enabled the investigation of fundamental CMS properties. Using monodisperse CMS, the dependence of the ζ-potential of CMS on the diameter was revealed. Colloidal crystals composed of mesoporous silica nanoparticles were fabricated by drying the colloidal solution. This is the first report regarding the fabrication of colloidal crystals composed of mesoporous silica nanoparticles with a small particle size.

Topography-driven bionano-interactions on colloidal silica nanoparticles

We report here that the surface topography of colloidal mesoporous silica nanoparticles (MSNs) plays a key role on their bionano-interactions by driving the adsorption of biomolecules on the nanoparticle through a matching mechanism between the surface cavities characteristics and the biomolecules stereochemistry. This conclusion was drawn by analyzing the biophysicochemical properties of colloidal MSNs in the presence of single biomolecules, such as alginate or bovine serum albumin (BSA), as well as dispersed in a complex biofluid, such as human blood plasma. When dispersed in phosphate buffered saline media containing alginate or BSA, monodisperse spherical MSNs interact with linear biopolymers such as alginate and with a globular protein such as bovine serum albumin (BSA) independently of the surface charge sign (i.e. positive or negative), thus leading to a decrease in the surface energy and to the colloidal stabilization of these nanoparticles. In contrast, silica nanoparticles with irregular surface topographies are not colloidally stabilized in the presence of alginate but they are electrosterically stabilized by BSA through a sorption mechanism that implies reversible conformation changes of the protein, as evidenced by circular dichroism (CD). The match between the biomolecule size and stereochemistry with the nanoparticle surface cavities characteristics reflects on the nanoparticle surface area that is accessible for each biomolecule to interact and stabilize any non-rigid nanoparticles. On the other hand, in contact with variety of biomolecules such as those present in blood plasma (55%), MSNs are colloidally stabilized regardless of the topography and surface charge, although the identity of the protein corona responsible for this stabilization is influenced by the surface topography and surface charge. Therefore, the biofluid in which nanoparticles are introduced plays an important role on their physicochemical behavior synergistically with their inherent characteristics (e.g., surface topography).

Construction of Homogenous/Heterogeneous Hollow Mesoporous Silica Nanostructures by Silica-Etching Chemistry: Principles, Synthesis, and Applications

Colloidal hollow mesoporous silica nanoparticles (HMSNs) are aspecial type of silica-based nanomaterials with penetrating mesopore channels on their shells. HMSNs exhibit unique structural characteristics useful for diverse applications: Firstly, the hollow interiors can function as reservoirs for enhanced loading of guest molecules, or as nanoreactors for the growth of nanocrystals or for catalysis in confined spaces. Secondly, the mesoporous silica shell enables the free diffusion of guest molecules through the intact shell. Thirdly, the outer silica surface is ready for chemical modifications, typically via its abundant Si-OH bonds. As early as 2003, researchers developed a soft-templating methodto prepare hollow aluminosilicate spheres with penetrating mesopores in a cubic symmetry pattern on the shells. However, adapting this method for applications on the nanoscale, especially for biomedicine, has proved difficult because the soft templating micelles are very sensitive to liquid environments, making it difficult to tune key parameters such as dispersity, morphology and structure. In this Account, we present the most recent developments in the tailored construction of highly dispersive and monosized HMSNs using simple silica-etching chemistry, and we discuss these particles' excellent performance in diverse applications. We first introduce general principles of silica-etching chemistry for controlling the chemical composition and the structural parameters (particle size, pore size, etching modalities, yolk-shell nanostructures, etc.) of HMSNs. Secondly, we include recent progress in constructing heterogeneous, multifunctional, hollow mesoporous silica nanorattles via several methods for diverse applications. These elaborately designed HMSNs could be topologically transformed to prepare hollow mesoporous carbon nanoparticles or functionalized to produce HMSN-based composite nanomaterials. Especially in biomedicine, HMSNs are excellent as carriers to deliver either hydrophilic or hydrophobic anti-cancer drugs, to tumor cells, offering enhanced chemotherapeutic efficacy and diminished toxic side effects. Most recently, research has shown that loading one or more anticancer drugs into HMSNs can inhibit metastasis or reverse multidrug resistance of cancer cells. HMSNs could also deliver hydrophobic perfluorohexane (PFH) molecules to improve high intensity focused ultrasound (HIFU) cancer surgery by changing the tissue acoustic environment; and HMSNs could act as nanoreactors for enhanced catalytic activity and/or durability. The versatility of silica-etching chemistry, a simple but scalable synthetic methodology, offers great potential for the creation of new types of HMSN-based nanostructures in a range of applications.