Modified Mesoporous Silica Nanoparticles Research Articles

Photo-induced surface grafting of phosphorylcholine containing copolymers onto mesoporous silica nanoparticles for controlled drug delivery

Surface modification of mesoporous silica nanoparticles (MSNs) with functional polymers has become one of the most interest topics over the last decade. Among various surface modification strategies, surface-initiated atom transfer radical polymerization (ATRP) has been regarded as one of the most effective methods. However, the typical ATRP strategy is relied on the transition metal ions and their organic ligands as the polymerization catalyst systems. In this work, a novel surface-initiated ATRP method was established for surface functionalization of MSNs using 10-Phenylphenothiazine (PTH) as the catalyst, 2-methacryloyloxyethyl phosphorylcholine (MPC) and itaconic acid (IA) as the monomers. We demonstrated that photo-induced ATRP is very effective for preparation of polymer functionalized MSNs (MSNs-NH2-poly(IA-co-MPC)). More importantly, MSNs-NH2-poly(IA-co-MPC) displayed well water dispersity, low cytotoxicity, high loading capability and controlled release behavior towards cisplatin. Furthermore, the method based on photo-induced surface-initiated ATRP could effectively overcome the drawbacks of conventional ATRP, which may involve in the residue of transition metal ions, high polymerization temperature, long polymerization term and complex experimental procedure. Therefore, this strategy described above is of great interest for fabrication of multifunctional polymer composites for various applications.

Preparation and controlled drug delivery applications of mesoporous silica polymer nanocomposites through the visible light induced surface-initiated ATRP

The mesoporous materials with large pore size, high specific surface area and high thermal stability have been widely utilized in a variety of fields ranging from environmental remediation to separation and biomedicine. However, surface modification of these silica nanomaterials is required to endow novel properties and achieve better performance for most of these applications. In this work, a new method has been established for surface modification of mesoporous silica nanoparticles (MSNs) that relied on the visible light induced atom transfer radical polymerization (ATRP). In the procedure, the copolymers composited with itaconic acid (IA) and poly(ethylene glycol)methyl acrylate (PEGMA) were grafted from MSNs using IA and PEGMA as the monomers and 10-Phenylphenothiazine(PTH) as the organic catalyst. The successful preparation of final polymer nanocomposites (named as MSNs-NH2-poly(IA-co-PEGMA)) were evidenced by a series of characterization techniques. More importantly, the anticancer agent cisplatin can be effectively loaded on MSNs-NH2-poly(IA-co-PEGMA) and controlled release it from the drug-loading composites with pH responsive behavior. As compared with conventional ATRP, the light induced surface-initiated ATRP could also be utilized for preparation of various silica polymer nanocomposites under rather benign conditions (e.g. absent of transition metal ions, low polymerization temperature and short polymerization time). Taken together, we have developed a rather promising strategy method for fabrication of multifunctional MSNs-NH2-poly(IA-co-PEGMA) with great potential for biomedical applications.

Layer-by-layer construction of lipid bilayer on mesoporous silica nanoparticle to improve its water suspensibility and hemocompatibility

Mesoporous silica nanoparticle was expected to provide a versatile drug delivery platform with modification flexibility. To improve its hemocompatibility and realize controlled and/or targeting drug release, modification of bare mesoporous silica nanoparticles is essential. Herein, a novel method of coating mesoporous silica nanoparticles with lipid bilayers was developed. First, a homemade organosiloxane precursor was used for hydrophobic modification of mesoporous silica nanoparticles, then phospholipids (1,2-dihexadecanoyl-sn-glycero-3-phosphocholine and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)]) were coated by a filming-rehydration method based on hydrophobic interaction. The nanoparticle samples were characterized by transmission electron microscope, dynamic light scattering, nitrogen sorption, Fourier transform infrared, and thermal gravimetric analysis. Furthermore, the novel lipid bilayer coated mesoporous silica nanoparticles were compared with bare mesoporous silica nanoparticles in terms of suspension stability, drug release, hemolysis, and nonspecific protein absorption. Our data proved that lipid bilayer coated mesoporous silica nanoparticles had better hemobiocompatibility and controlled drug release properties than that of bare mesoporous silica nanoparticles.

Multifunctional Redox-Responsive Mesoporous Silica Nanoparticles for Efficient Targeting Drug Delivery and Magnetic Resonance Imaging.

The convenient modification of mesoporous silica nanoparticles (MSN) can provide great opportunities for constructing a new generation of nanocarriers with multiple functions. In the current study, we fabricated a new multifunctional drug delivery system based on MSN capped by gadolinium-based bovine serum albumin complex (BSA-Gd) and hyaluronic acid (HA) via reductive-cleavable disulfide bond. In this multifunctional nanoparticle (MSN-ss-GHA), BSA-Gd component was prepared by biomineralization and acted as both smart gatekeeper and contrast agent for magnetic resonance (MR) imaging, while HA served as the targeted molecule to improve the specific affinity of MSN-ss-GHA toward cancer cells. The successful fabrication of MSN-ss-GHA was demonstrated by a series of physicochemical characterization. The redox-sensitive drug release behavior of doxorubicin hydrochloride (DOX) loaded MSN-ss-GHA (DOX@MSN-ss-GHA) was also verified. Comparatively, the MSN-ss-GHA exhibited excellent biocompatibility and distinctly enhanced cell uptake by 4T1 cells. More importantly, the improved in vitro MR imaging ability of MSN-ss-GHA over that of Gd-DTPA was also confirmed. The results also suggested that the DOX@MSN-ss-GHA could efficiently deliver DOX into 4T1 cells and showed enhanced cytotoxicity as compared to that of nontargeted nanocarrier. The in vivo experiment also demonstrated the negligible toxicity of MSN-ss-GHA and improved antitumor suppression of DOX@MSN-ss-GHA. Thus, this multifunctional MSN-based theranostic agent holds potential for efficient redox-responsive targeting drug delivery and MR imaging.

Tailored Mesoporous Silica Nanoparticles for Controlled Drug Delivery: Platform Fabrication, Targeted Delivery, and Computational Design and Analysis.

Mesoporous silica nanoparticles (MSNs) are exceptionally promising drug carriers for controlled drug delivery systems because their morphology, pore structure, pore volume and pore size can be well tailored to obtain certain drug release profiles. Moreover, they possess the ability to specifically transport and deliver anti-cancer drugs when targeting molecules are properly grafted onto their surface. MSNs based drug delivery systems have the potential to revolutionize cancer therapy. This review provides a comprehensive overview of the fabrication, modification of MSNs and their applications in tumour-targeted delivery. In addition, the characterization and analysis of MSNs with computer aided strategies were described. The existing issues and future prospective concerning the applications of MSNs as drug carriers for controlled drug delivery systems were discussed.

Polydopamine-based surface modification of mesoporous silica nanoparticles as pH-sensitive drug delivery vehicles for cancer therapy

A novel pH-sensitive drug delivery system of mesoporous silica nanoparticles (MSNs) which were modified by polydopamine (PDA) for controlled release of cationic amphiphilic drug desipramine (DES) was prepared. MSNs–DES–PDA were characterized in terms of size, size distribution, surface morphology, BET surface area, mesoporous size and pore volume, drug loading content and in vitro drug release profile. MSNs–DES–PDA had high drug loading content and pH sensitivity. The DES release profiles of MSNs–DES and MSNs–DES–PDA were totally different, and the drug release of MSNs–DES–PDA accelerated with increasing acidity. MSNs–DES–PDA can be internalized into cells. In vitro experiments demonstrated that MSNs–DES–PDA had higher cytotoxicity and inhibitory effects on acid sphingomyelinase than those of free DES. This drug delivery system was beneficial for controlled release and cancer therapy.

Simultaneous removal of Pb(II) and 2,4,6-trichlorophenol by a hierarchical porous PU@PDA@MSNs sponge with reversible “shape memory” effect

A hierarchical porous PU@PDA@MSNs sponge with reversible “shape memory” effect was employed in this investigation for the simultaneous adsorption of Pb(II) and 2,4,6-trichlorophenol (TCP). Our strategy was based on facile conjugation of carboxyl groups modified mesoporous silica nanoparticles (MSNs) to poly(dopamine) (PDA) coated polyurethane (PU) sponge (PU@PDA), and the as-prepared PU@PDA@MSNs sponge possessed the advantages of less operation time, convenient adsorbent collection and regeneration owing to its reversible “shape memory” effect. In single system, Pb(II) and TCP adsorption were implemented at pH=6.0, and their max monolayer adsorption amount at 298k were 104.2mgg−1 and 184.2mgg−1, respectively. However, the binary system exhibited that the coexistence of Pb(II) and TCP could obviously accelerate jointly adsorption at low concentrations, due to partial complexation between Pb(II) and TCP during the 10–30mgL−1 of Pb(II) and TCP. While at higher concentrations, TCP adsorption was inhibited in relation to the competition from Pb(II), but Pb(II) adsorption was scarcely affected due to its smaller size and strong complexation with amino groups from PU@PDA@MSNs sponge. The PU@PDA sponge could be simply recycled and maintained stability after seven adsorption/desorption cycles in the regeneration steps.

Combined Spectroscopic and Calorimetric Studies to Reveal Absorption Mechanisms and Conformational Changes of Protein on Nanoporous Biomaterials.

In this study the effect of surface modification of mesoporous silica nanoparticles (MSNs) on its adsorption capacities and protein stability after immobilization of beta-lactoglobulin B (BLG-B) was investigated. For this purpose, non-functionalized (KIT-6) and aminopropyl-functionalized cubic Ia3d mesoporous silica ([n-PrNH2-KIT-6]) nanoparticles were used as nanoporous supports. Aminopropyl-functionalized mesoporous nanoparticles exhibited more potential candidates for BLG-B adsorption and minimum BLG leaching than non-functionalized nanoparticles. It was observed that the amount of adsorbed BLG is dependent on the initial BLG concentration for both KIT-6 and [n-PrNH2-KIT-6] mesoporous nanoparticles. Also larger amounts of BLG-B on KIT-6 was immobilized upon raising the temperature of the medium from 4 to 55 °C while such increase was undetectable in the case of immobilization of BLG-B on the [n-PrNH2-KIT-6]. At temperatures above 55 °C the amounts of adsorbed BLG on both studied nanomaterials decreased significantly. By Differential scanning calorimetry or DSC analysis the heterogeneity of the protein solution and increase in Tm may indicate that immobilization of BLG-B onto the modified KIT-6 results in higher thermal stability compared to unmodified one. The obtained results provide several crucial factors in determining the mechanism(s) of protein adsorption and stability on the nanostructured solid supports and the development of engineered nano-biomaterials for controlled drug-delivery systems and biomimetic interfaces for the immobilization of living cells.

Light- and pH-activated intracellular drug release from polymeric mesoporous silica nanoparticles

Surface modified mesoporous silica nanoparticles (MSNs) with reduced toxicity were prepared for light and pH dual triggerable drug delivery system. Both 413nm light and acidic environment can activate the drug release process, improving the pharmacological action. By applying rhodamine B (RhB) as a model drug, the accumulative RhB release is as high as 95% in pH 5.0 and in irradiation of 413nm light, compared to only 55% in pH 7.4 and in dark. The anti-cancer drug camptothecin (CPT) loaded nanoparticles can kill cancer cells with IC50 value of 0.02μgmL−1 in exposure of 413nm light, which is much lower than free CPT (about 0.1μgmL−1). Multimodal nonlinear optical imaging microscopy (NLOM) was employed to acquire in vitro coherent anti-Stokes Raman (CARS) and two-photon excited fluorescence (TPEF) images of live MCF-7 cells and showed that the nanoparticles can be taken up by breast tumor cell MCF-7 with high efficiency, indicating its great potential for anti-cancer drug delivery system.

Cancer Nanomedicine: Cationic Polymer Modified Mesoporous Silica Nanoparticles for Targeted siRNA Delivery to HER2+ Breast Cancer (Adv. Funct. Mater. 18/2015)

Cancer Nanomedicine: Cationic Polymer Modified Mesoporous Silica Nanoparticles for Targeted siRNA Delivery to HER2⁺ Breast Cancer (Adv. Funct. Mater. 18/2015)

Cationic Polymer Modified Mesoporous Silica Nanoparticles for Targeted SiRNA Delivery to HER2+ Breast Cancer.

In vivo delivery of siRNAs designed to inhibit genes important in cancer and other diseases continues to be an important biomedical goal. We now describe a new nanoparticle construct that has been engineered for efficient delivery of siRNA to tumors. The construct is comprised of a 47-nm mesoporous silica nanoparticle (MSNP) core coated with a cross-linked PEI-PEG copolymer, carrying siRNA against the HER2 oncogene, and coupled to the anti-HER2 monoclonal antibody (trastuzumab). The construct has been engineered to increase siRNA blood half-life, enhance tumor-specific cellular uptake, and maximize siRNA knockdown efficacy. The optimized anti-HER2-nanoparticles produced apoptotic death in HER2 positive (HER2+) breast cancer cells grown in vitro, but not in HER2 negative (HER2-) cells. One dose of the siHER2-nanoparticles reduced HER2 protein levels by 60% in trastuzumab-resistant HCC1954 xenografts. Multiple doses administered intravenously over 3 weeks significantly inhibited tumor growth (p < 0.004). The siHER2-nanoparticles have an excellent safety profile in terms of blood compatibility and low cytokine induction, when exposed to human peripheral blood mononuclear cells. The construct can be produced with high batch-to-batch reproducibility and the production methods are suitable for large-scale production. These results suggest that this siHER2-nanoparticle is ready for clinical evaluation.

An efficient rose bengal based nanoplatform for photodynamic therapy.

Organically modified mesoporous silica nanoparticles (MSNs) containing rose bengal (RB), a xanthene dye, were successfully synthesized. RB-modified MSNs have shown a relevant photostability and a high efficiency in the photoproduction and delivery of singlet oxygen ((1)O2), which is particularly promising for photodynamic therapy (PDT) applications. In vitro tests have evidenced that RB-MSNs are able to reduce cell proliferation in one of the most aggressive skin cancer types (SK-MEL-28) after green-light irradiation.

Curcumin-loaded guanidine functionalized PEGylated I3ad mesoporous silica nanoparticles KIT-6: Practical strategy for the breast cancer therapy

In this research, we have synthesized guanidine functionalized PEGylated mesoporous silica nanoparticles as a novel and efficient drug delivery system (DDS). For this purpose, guanidine functionalized PEGylated I3ad mesoporous silica nanoparticle KIT-6 [Gu@PEGylated KIT-6] was utilized as a promising system for the effective delivery of curcumin into the breast cancer cells. The modified mesoporous silica nanoparticles (MSNs) was fully characterized by different techniques such as transmission and scanning electron microscopy (TEM & SEM), N2 adsorption-desorption measurement, thermal gravimetric analysis (TGA), X-ray powder diffraction (XRD), and dynamic light scattering (DLS). The average particle size of [Gu@PEGylated KIT-6] and curcumin loaded [Gu@PEGylated KIT-6] nanoparticles were about 60 and 70 nm, respectively. This new system exhibited high drug loading capacity, sustained drug release profile, and high and long term anticancer efficacy in human cancer cell lines. It showed pH-responsive controlled characteristics and highly programmed release of curcumin leading to the satisfactory results in in vitro breast cancer therapy. Our results depicted that the pure nanoparticles have no cytotoxicity against human breast adenocarcinoma cells (MCF-7), mouse breast cancer cells (4T1), and human mammary epithelial cells (MCF10A).

Oral glucose- and pH-sensitive nanocarriers for simulating insulin release in vivo

We design novel oral glucose sensitive nanocarriers for simulating insulin release using a modification of mesoporous silica nanoparticles (MSN) surfaces with a sensitive shell and conduct in vivo testing of these nanocarriers in diabetic rats. Here, MSN are coated with pH-sensitive dextran–maleic acid (Dex–Ma) and then grafted with glucose-sensitive 3-amidophenylboronic acid (APBA). These core–shell nanocarriers are confirmed by FT-IR, TEM, TGA, N2 adsorption–desorption method and elemental analysis. The results indicate that the MSN core can efficiently increase the loading capacity of insulin. In vitro insulin release shows good glucose-trigged behavior, in addition the rate of insulin release can be easily adjusted by changing the shell thickness. The cell viability of the nanocarriers against calu-3 cells demonstrates excellent cytocompatibility, and the nanocarriers can be internalized into cells. According to the studies of diabetic rats in vivo, the oral insulin-loaded nanocarriers produce an obvious hypoglycemic effect compared with insulin directly given orally. Study of the ligated intestinal loops absorption indicates that the material can enhance the permeation of insulin across the epidermis of intestine and facilitate the uptake of insulin. Therefore, the simple and effective pH- and glucose-sensitive nanocarrier can be regarded as a potential self-regulated tool to simulate insulin release in vivo.

A combined "RAFT" and "Graft From" polymerization strategy for surface modification of mesoporous silica nanoparticles: towards enhanced tumor accumulation and cancer therapy efficacy.

A novel modification route integrating the copolymers of positive charged quaternary amines and polyethylene glycol (PEG) units using a combination of reversible addition-fragmentation chain-transfer polymerization (RAFT) and "Graft From" strategy, has been proposed and developed, for the first time, to decorate the surface of mesoporous silica nanoparticles (MSNs). These MSNs are shown to have a greatly reduced hydrodynamic particle size in physiological solution. It is demonstrated that such an efficient copolymer surface modification strategy, resulting in PEG coating with high positive zeta potential, can achieve a nearly 2-fold enhanced permeability and retention (EPR) effect, and longer blood half-life compared to coating with PEG only. Besides, the in vivo results demonstrated that this surface modification strategy could lead to a higher efficacy of doxorubicin (DOX) drug delivery and greater suppression of side effects compared to the free drug. Based on this novel strategy of combining "RAFT" and "Graft From" polymerization, it is anticipated that this efficient modification of tumor-specific targeting of MSNs can be widely used in future nanomedicine research.

Synthesis and surface modification of mesoporous silica nanoparticles and its application as carriers for sustained drug delivery

High drug loading is one of the important issues in the drug delivery research, especially the drug delivery system by oral administration. If high drug loading carriers are utilized the times of drug intake could be significantly reduced. Accordingly in this study, ordered mesoporous SBA-15 modified with (3-aminopropyl) triethoxysilane (APTES) was used as a carrier for nonsteroidal anti-inflammatory drug and optimization of the loading process was done. SBA-15 silica material with rope-like morphology was synthesized and modified by post-synthesis method with APTES. The synthesized SBA-15 and modified SBA-15 were characterized by XRD, SEM, thermal analysis and FT-IR spectroscopy. Loading optimization experiments were performed by changing the factors affecting the drug loading, such as temperature, time, stirring rate, Ibuprofen/SBA-15 ratio. The results of drug delivery experiments showed that the surface modification of SBA-15 with amino groups significantly increases the drug loading and decreases the drug delivery rate.

Characterization and Modification of Mesoporous Silica Nanoparticles Prepared by Sol-Gel

Mesoporous silica nanoparticles (MSNs) were synthesized by sol-gel reaction at normal pressure by using TEOS as a silica source and CTAB as a directing agent in ammonia solution at 323 K subsequently calcined at 823 K. Then inorganic pores were modified with metal-supported MSN with attention to the acidity, surface area, pore size, and ability of ion exchange. Crystalline size was shown to decrease up to 20 molar ratios of Si/Al followed by increasing while further adding nanoparticles-aluminium. Moreover, the XRD patterns revealed the mesostructured material for all with 2D hexagonal structure. The obtained results from the XRD patterns were confirmed by using BET and EDX. The BET surface areas revealed the spherical shape for all samples with a decrease in the pore volume and surface area for various AlMSNs which emphasized that the loading of Al and was compatible with XRD results. MSN was prepared by sol-gel methods followed by loading of Al in order to prepare AlMSN which possess strong Lewis acidic sites. This modification occurred by using various molar ratios of 0, 5, 10, 20, 50, and 100 Si/Al, respectively. The XRD patterns of various ratios of Si/Al were interpreted in terms of strain, nanocrystalline size, and distribution of the particle size by deriving Wiliamson Hall equation.

The eradication of breast cancer cells and stem cells by 8-hydroxyquinoline-loaded hyaluronan modified mesoporous silica nanoparticle-supported lipid bilayers containing docetaxel

Breast cancer stem cells (BCSCs), which can fully recapitulate the tumor origin and are often resistant to chemotherapy and radiotherapy, are currently considered as a major obstacle for breast cancer treatment. To achieve the goal of both targeting BCSCs and bulk breast cancer cells, we developed 8-hydroxyquinoline-loaded hyaluronan modified mesoporous silica nanoparticles (MSN)-supported lipid bilayers (HA-MSS) and docetaxel-loaded MSS. The results showed that the size of all the nanoparticles was smaller than 200 nm. BCSCs were enriched from MCF-7 cells by a sphere formation method and identified with the CD44+/CD24− phenotype. Quantitative and qualitative analysis demonstrated that HA promotes the uptake of HA-MSS in CD44-overexpressing MCF-7 mammospheres, revealing the mechanism of receptor-mediated endocytosis. DTX or DTX-loaded MSS showed much enhanced cytotoxicity against MCF-7 cells compared with MCF-7 mammospheres, whereas 8-HQ or 8-HQ-loaded HA-MSS showed much enhanced cytotoxicity against MCF-7 mammospheres compared with MCF-7 cells. In the MCF-7 xenografts in mice, the combination therapy with DTX-loaded MSS plus 8-HQ-loaded HA-MSS produced the strongest antitumor efficacy, with little systemic toxicity (reflecting by loss of body weight) in mice. Thus, this combination therapy may provide a potential strategy to improve the therapy of breast cancer by eradication of breast cancer cells together with BCSCs.

Hyaluronic acid modified mesoporous silica nanoparticles for targeted drug delivery to CD44-overexpressing cancer cells

In this paper, a targeted drug delivery system has been developed based on hyaluronic acid (HA) modified mesoporous silica nanoparticles (MSNs). HA-MSNs possess a specific affinity to CD44 over-expressed on the surface of a specific cancer cell line, HCT-116 (human colon cancer cells). The cellular uptake performance of fluorescently labelled MSNs with and without HA modification has been evaluated by confocal microscopy and fluorescence-activated cell sorter (FACS) analysis. Compared to bare MSNs, HA-MSNs exhibit a higher cellular uptake via HA receptor mediated endocytosis. An anticancer drug, doxorubicin hydrochloride (Dox), has been loaded into MSNs and HA-MSNs as drug delivery vehicles. Dox loaded HA-MSNs show greater cytotoxicity to HCT-116 cells than free Dox and Dox-MSNs due to the enhanced cell internalization behavior of HA-MSNs. It is expected that HA-MSNs have a great potential in targeted delivery of anticancer drugs to CD44 over-expressing tumors.

Synthesis and Characterization of pH‐Sensitive Positive‐charge Silica Nanoparticles for Oral Anionic Drug Delivery

AbstractThe objective of this study is to utilize the pH sensitivity of modified mesoporous silica nanoparticles (MSN) for oral drug delivery. In the first time, a pH‐sensitive ionic liquid was synthesized through the quaternization of 3‐aminopropyltrimethoxysilane (3‐ATMS) with sodium monochloroacetate (SMCA). Then, silica nanoparticle was modified by this pH‐sensitive ionic liquid and converted to a pH‐sensitive positive‐charge silica nanoparticle (PCSN). The nanoparticle was characterized by FTIR and SEM. Naproxen as anionic drug molecules was entrapped in this pH‐sensitive positive‐charge silica nanoparticles (PCSN) and the in vitro release profiles were established separately in both (SGF, pH 1) and (SIF, pH 7.4).