Amino-functionalized Mesoporous Silica Nanoparticles Research Articles

Synthesis of pH-sensitive poly(β-amino ester)-coated mesoporous silica nanoparticles for the controlled release of drugs

This report describes the synthesis of a controlled drug delivery system that was obtained by coating mesoporous silica nanoparticles (MSNs) with poly(β-amino ester) (PbAE), which is a solid and stable material at physiological pH, but is dissolved at acidic pH values, such as those in tumor tissues (from 5.0 to 6.5). To synthesize the system, PbAE chains were grafted onto amino-functionalized MSNs through a reaction between the surface amino groups of MSNs and the ends of acrylate chains of a PbAE. The system was physicochemically characterized by dynamic light scattering (DLS), Fourier transform infrared spectroscopy, transmission electron microscopy, thermogravimetric analysis, X-ray photoelectron spectrometry, and X-ray diffraction analyses. In addition, the in vitro release of doxorubicin (DOX) and doxycycline (DXY) in acidic and physiological media was evaluated. It was observed that the PbAE modification did not affect the mesoporous structure of MSNs. When the amount of 3-aminopropyltriethoxysilane was increased during functionalization, the amount of PbAE binding to MSNs increased as well. With respect to drug release, the sample with the highest amount of PbAE showed better control in the delivery of DXY and DOX in acidic media, because at pH 5.5, the release of both drugs was 40% higher than that at pH 7.4. These results reveal two aspects about the presence of PbAE in MSNs: PbAE does not affect the mesoporous structure of the nanoparticles, and PbAE is the main factor controlling the delivery of drugs in acidic media.

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.

Amino-functionalized mesoporous silica nanoparticles as efficient carriers for anticancer drug delivery.

Amino-functionalized mesoporous silica nanoparticles (MSN-NH2) were synthesized by a post-grafting method and further studied as carriers for doxorubicin hydrochloride (DOX) delivery. The morphology, structure, and property of MSN-NH2 and DOX-loaded MSN-NH2 (DOX@MSN-NH2) were studied using various techniques, such as transmission electron microscopy, Fourier transformed infrared spectroscopy, N2 adsorption-desorption isotherms, and zeta potentials. The drug loading and release profile as well as the invitro cell cytotoxicity were detaily investigated. The results indicated that the loading content of DOX increased with the decrease of MSN-NH2/DOX mass ratio and/or the increase of amino density. DOX@MSN-NH2 exhibited a pH-dependent drug release, drug release increased as the pH value decreased. Compared with MSN-NH2, which were neglectable cytotoxicity against non-small-cell lung cancer (A549) cells, DOX@MSN-NH2 displayed remarkable cytotoxicity toward A549 cells in dose- and time-dependent manners. It was concluded that the as-synthesized MSN-NH2 could be used as promising drug carriers for cancer therapy.

PH-Responsive Core-Shell Structured Nanoparticles for Triple-Stage Targeted Delivery of Doxorubicin to Tumors.

The application of cytotoxic chemotherapeutics in cancer therapy has been largely restricted by their lack of selectivity. Despite the existence of numerous targeted delivery systems, it is practically challenging to develop one single system to simultaneously cover tumor-targeted delivery of chemotherapeutics at the tissue, cellular, and subcellular levels. To solve this problem, pH-responsive core-shell structured nanoparticles (CSNPs) were self-assembled in this study to provide triple-stage targeted delivery of doxorubicin (DOX) from the injection site to the nuclei of cancer cells. Amino-functionalized mesoporous silica nanoparticles (MSN) were doubly modified with TAT peptide and acid-cleavable polyethylene glycol (PEG) as the DOX-loaded cationic core. The anionic shell was constituted by galactose-modified poly(allylamine hydrochloride)-citraconic anhydride, a hepato-carcinoma-targeting polymer with charge-reversible property. In vitro results showed that PEG effectively reduced protein adsorption and phagocytic capture of CSNPs in the circulating blood (pH 7.4), thus facilitating passive accumulation in tumors (tissue level). Following PEG detachment via acidic hydrolysis in tumor microenvironment (pH 6.5), the exposed galactose ligands endowed CSNPs with active internalization into hepato-carcinoma cells (cellular level). Afterward, the acidity in endosomes and lysosomes (pH 5.0) triggered the conversion of anionic shell into positive charges, leading to core-shell disassembly and subsequent TAT-mediated delivery of DOX to the nuclei (subcellular level). Importantly, the efficiencies of each targeting moiety were nicely preserved when combining together in CSNPs. As a result, improved tumorous distribution and potent therapeutic efficacy of CSNPs were noted in tumor-bearing mice at a relatively low dose. CSNPs therefore provide an efficient and nontoxic platform for the targeted delivery of antitumor drugs.

Co-delivery of erlotinib and doxorubicin by pH-sensitive charge conversion nanocarrier for synergistic therapy

Pretreatment of lung cancer cells with epidermal growth factor receptor (EGFR) inhibitor erlotinib has been recently reported that could dramatically synergize their apoptotic response to DNA damage agent doxorubicin (DOX). To translate this synergistic therapy into in vivo anticancer therapy and clinical practice, we designed a novel pH-sensitive charge conversion nanocarrier (M-HHG2C18-L) that contained erlotinib/DOX combination and produced a sequential staggered drug release for synergistic lung cancer therapy. In this study, a synthetic zwitterionic oligopeptide lipid (1,5-dioctadecyl-l-glutamyl2-histidyl-hexahydrobenzoic acid, HHG2C18) was used to construct a pH-sensitive lipid bilayer (HHG2C18-L), which was subsequently applied to coat amino-functionalized mesoporous silica nanoparticles (MSN-NH2). Erlotinib and DOX were separately incorporated into HHG2C18-L and MSN-NH2 respectively to obtain pH-sensitive charge conversion erlotinib/DOX co-delivery nanoparticles (M-HHG2C18-L(E+D)). We confirmed that M-HHG2C18-L(E+D) were able to reverse surface zeta potential from negative to positive at tumor extracellular pH, thus facilitating the targeted cancer cell internalization. Furthermore, as erlotinib was sequestered in the exterior lipid bilayer and the controlled release ability of MSN-NH2, erlotinib released faster than DOX during the cellular transport. Additionally, HHG2C18-L became more positive at tumor intracellular pH and enhanced Coulombic repulsion with MSN-NH2, leading to increased sequential staggered release of erlotinib and DOX. Due to the pretreatment and time-staggered inhibition of EGFR with erlotinib and the enhanced intracellular release of DOX to the nucleus, the maximized synergistic cell killing effect was achieved. Compared to non-sensitive erlotinib/DOX co-delivery nanoparticles (M-SPC-L(E+D)) and simultaneous DRUG coadministration. M-HHG2C18-L(E+D) with sequential staggered drug release and pH-sensitive charge conversional properties showed great synergistic effects in antiproliferation and apoptosis of A549 human cancer cells in vitro. The in vivo study demonstrated that M-HHG2C18-L(E+D) exhibited considerable tumor accumulation and potent suppression of tumor growth in Lewis lung carcinoma tumor bearing mice. It was also demonstrated that M-HHG2C18-L(E+D) showed no systemic toxicity and possessed distinguished effect on extending survival period. These results suggested that M-HHG2C18-L(E+D) had great potential application in cancer treatment.

Control of particle uptake kinetics from particulate mesoporous silica films by cells through covalent linking of particles to the substrate - towards sequential drug delivery for tissue engineering applications.

A sequential release of biological cues is of high interest in tissue engineering applications, as both the proliferation and the differentiation of stem cells can be drugged. In previous studies we have shown that particulate films of mesoporous silica particles can be successfully applied for influencing stem cell fates through intracellular drug delivery after particle internalisation by the cells. In this study, we develop this concept towards an enhanced control of the particle uptake kinetics through either adsorption or covalent linking of the mesoporous silica particles to the substrate. Microscopy glass slides were initially functionalized by an aminosilane to which a thin layer of hyaluronic acid was covalently attached through an amide bond. A sub-monolayer of amino-functionalized mesoporous silica nanoparticles with a diameter of 400 nm were then adsorbed to the hyaluronic acid-functionalized surface by adsorption under high-shear conditions. Subsequently, the adsorbed particles were covalently linked to the hyaluronic acid through an amide bond. Corresponding films without the covalent coupling step were used as the control. Muscle stem cells attach and proliferate nicely on all films, and do internalize particles in all cases. However, the kinetics of particle internalization was clearly delayed for the covalently attached particles in comparison to physisorbed particles. Thus, the results imply that tuning of the particle-substrate interactions through linking chemistries is a promising means of achieving sequential particle-mediated drug release from films and that corresponding chemistries should also be applicable for 3D scaffold systems.

Electrochemiluminescence immunoassay using a paper electrode incorporating porous silver and modified with mesoporous silica nanoparticles functionalized with blue-luminescent carbon dots

We have prepared carbon dots (C-dots) by pyrolysis of citric acid. The one-pot synthetic strategy is time-saving and simple and the resulting C-dots display blue luminescence with high quantum yield at an anodic potential of +0.6 V. An electrochemiluminescence (ECL) immunoassay was designed for the sensitive determination of cancer antigen 125 (CA125) by using amino-functionalized mesoporous silica nanoparticles (NH2-MSNs) capped with C-dots. These act as amplification labels on a novel kind of paper working electrode modified with silver nanoparticles (Ag-PWE). This electrode was fabricated by a seed-mediated growth approach and served as a support for the attachment of the antibody. The NH2-MSNs possess higher volume-to-surface ratio than the solid nanoparticles that can carry more C-dots which improves the sensitivity of the immunoassay. The ECL immunoassay was operated by using triethanolamine as a coreactant that is less toxic and more soluble than other popular coreactants. The assay has a linear response over a wide range of 0.01–50 U mL−1, and the detection limit is 4.3 mU mL−1. This makes the method one of the most sensitive assays for CA125.

Amino-functionalized mesoporous silica nanoparticles: adsorption and protection for pcDNA3.1(+)-PKB-HA

This work evaluated the adsorption and protection capacities of amino-functionalized mesoporous silica nanoparticles (Am-MSNs) for the recombinant DNA (rDNA), pcDNA3.1(+)-PKB-HA. The in vitro biocompatibility of Am-MSNs was also tested on HeLa and A549 cells, respectively. The results reveal that the MSNs modified with 3-aminopropyltriethoxysilane exhibit good adsorption capacity for pcDNA3.1(+)-PKB-HA at physiological conditions and the adsorption amount is higher than that of other silica nanoparticles. Moreover, the material can also protect pcDNA3.1(+)-PKB-HA from enzymatic degradation completely and presents high in vitro biocompatibility. This demonstrates that Am-MSNs may be potential nonviral vector candidates for pcDNA3.1(+)-PKB-HA.

Study of amino-functionalized mesoporous silica nanoparticles (NH2-MSN) and polyamide-6 nanocomposites co-incorporated with NH2-MSN and organo-montmorillonite

In this work, spherical mesoporous silica nanospheres (MSNs) functionalized by content-tunable amino groups were synthesized via a facile co-condensation method aided by both ionic and nonionic surfactants. 3-Aminopropyltrimethoxysilane (APTMS) was added to co-condense with tetraethyl orthosilicate in basic aqueous solution at varied concentration, obtaining different surface amino content. The influence of APTMS concentration on the morphology, pore structure and surface amino coverage of synthesized nanoparticles was systematically investigated. A decelerating trend of the “surface amino coverage” growing with increasing “APTMS concentration” was observed, indicating there is a maximum grafting limit for APTMS on the exterior MSN surface. For the first time, MSN containing amino group (NH2-MSN) was utilized as inorganic nanofiller in polyamide-6 (PA6) nanocomposites, prepared by incorporating NH2-MSN and organo-montmorillonite (OMMT) simultaneously in PA6 through melt compounding. Mechanical properties of PA6 nanocomposites were fully investigated at two widely varied strain-rates (quasi-static and high-speed). The PA6/NH2-MSN/OMMT ternary nanocomposite showed simultaneous improvement of tensile stiffness (Young’s modulus and maximum tensile stress) and ductility (elongation at break). PA6-MSN interface analysis indicated that the strong interfacial affinity (covalent binding) may confine the mobility of PA6 molecules along the tension axis and obstruct the growing/propagation of micro-cracks. However, the synergistic effect involving nanofillers of different shape (spherical NH2-MSN and platelet OMMT) was considered to play critical role for the uniquely improved tensile ductility of ternary nanocomposite.