Modified Mesoporous Silica Nanoparticles Research Articles

Surface Modification of Mesoporous Silica Nanoparticles as a Means to Introduce Inherent Cancer‐Targeting Ability in a 3D Tumor Microenvironment

Mesoporous silica nanoparticles (MSNs) have emerged as promising drug carriers that can facilitate targeted anticancer drug delivery, but efficiency studies relying on active targeting mechanisms remain elusive. This study implements in vitro 3D cocultures, so‐called microtissues, to model a physiologically relevant tumor microenvironment (TME) to examine the impact of surface‐modified MSNs without targeting ligands on the internalization, cargo delivery, and cargo release in tumor cells and cancer‐associated fibroblasts. Among these, acetylated MSNs most effectively localized in tumor cells in a 3D setting containing collagen, while other MSNs did so to a lesser degree, most likely due to remaining trapped in the extracellular matrix of the TME. Confocal imaging of hydrophobic model drug‐loaded MSNs demonstrated effective cargo release predominantly in tumor cells, both in 2D and 3D cocultures. MSN‐mediated delivery of an anticancer drug in the microtissues exhibited a significant reduction in tumor organoid size and enhanced the tumor‐specific cytotoxic effects of a γ‐secretase inhibitor, compared to the highly hydrophobic drug in free form. This inherent targeting potential suggests reduced off‐target effects and increased drug efficacy, showcasing the promise of surface modification of MSNs as a means of direct cell‐specific targeting and delivery for precise and successful targeted drug delivery.

Surface Modification of Mesoporous Silica Nanoparticles for Application in Targeted Delivery Systems of Antitumour Drugs.

The problem of tumour therapy has attracted the attention of many researchers for many decades. One of the promising strategies for the development of new dosage forms to improve oncology treatment efficacy and minimise side effects is the development of nanoparticle-based targeted transport systems for anticancer drugs. Among inorganic nanoparticles, mesoporous silica deserves special attention due to its outstanding surface properties and drug-loading capability. This review analyses the various factors affecting the cytotoxicity, cellular uptake, and biocompatibility of mesoporous silica nanoparticles (MSNs), constituting a key aspect in the development of safe and effective drug delivery systems. Special attention is paid to technological approaches to chemically modifying MSNs to alter their surface properties. The stimuli that regulate drug release from nanoparticles are also discussed, contributing to the effective control of the delivery process in the body. The findings emphasise the importance of modifying MSNs with different surface functional groups, bio-recognisable molecules, and polymers for their potential use in anticancer drug delivery systems.

Advanced hybrid silica nanoparticles with pH-responsive diblock copolymer brushes: optimized design for controlled doxorubicin loading and release in cancer therapy.

This study delves into the development, characterization, and application of modified mesoporous silica nanoparticles (MSNs) for targeted drug delivery in cancer therapy. MSNs were functionalized with poly(2-(diisopropylamino)ethyl methacrylate) (PDPA) and poly(glycidyl methacrylate) (PGMA), and further modified with cross-linkers DAE and Ornithine. Characterization using FT-IR, SEM, TEM, DLS, and XPS confirmed the successful surface modifications, revealing particle sizes primarily within the 63-94 nm range. The MSNs demonstrated a pH-responsive behavior, crucial for smart drug delivery. Loading and release studies using Doxorubicin (DOX) showed a controlled release, with an 8 μg mg-1 loading capacity. Cytotoxicity assays on Caco2 colon cancer cells revealed that unloaded nano-systems, at concentrations above 45 μM, resulted in approximately 60% cell death, indicating inherent anti-cancer properties. However, variations in cytotoxic effects were observed in drug-loaded MSNs, with some modifications showing reduced anti-cancer activity. These findings highlight the potential of MSNs in drug delivery and cancer treatment, emphasizing the importance of nanoparticle design in therapeutic efficacy.

Utilization of Deoxycholic Acid Terminated L-cysteine Modified Mesoporous Silica Nanoparticles as a Nanoadsorbent for Removing Rhodamine B from Contaminated Water: Adsorption Equilibrium and Kinetic Studies

Utilization of Deoxycholic Acid Terminated L-cysteine Modified Mesoporous Silica Nanoparticles as a Nanoadsorbent for Removing Rhodamine B from Contaminated Water: Adsorption Equilibrium and Kinetic Studies

Aptamer-modified chitosan-capped mesoporous silica nanoparticles for co-delivery of cytarabine and daunorubicin in leukemia

In this study, surface modified mesoporous silica nanoparticles (MSNs) were prepared for the targeted delivery of the anticancer agents, daunorubicin (DNR) and cytarabine (CTR), against K562 leukemia cancer cell lines. The MSNs were surface-modified with pH-sensitive chitosan (CS) to prevent the burst release of anticancer agents at the physiological pH of 7.4 and to enable a higher drug release at lower pH and higher concentration of glutathione. Finally, the MSNs were surface modified with KK1B10 aptamer (Apt) to enhance their uptake by K562 cells through ligand-receptor interactions. The MSNs were characterized using different methods and both in vitro and in vivo experiments were utilized to demonstrate their suitability as targeted anticancer agents. The resultant MSNs exhibited an average particle size of 295 nm, a surface area of 39.06 m2/g, and a cumulative pore volume of 0.09 cm3/g. Surface modification of MSNs with chitosan (CS) resulted in a more regulated and acceptable continuous release rate of DNR. The drug release rate was significantly higher at pH 5 media enriched with glutathione, compared to pH 7.4. Furthermore, MSNs coated with CS and conjugated with aptamer (MSN-DNR + CTR@CS-Apt) exhibited a lower IC50 value of 2.34 µg/ml, compared to MSNs without aptamer conjugation, which displayed an IC50 value of 12.27 µg/ml. The results of the cell cycle analysis indicated that the administration of MSN-DNR + CTR@CS-Apt led to a significant increase in the population of apoptotic cells in the sub-G1 phase. Additionally, the treatment arrested the remaining cells in various other phases of the cell cycle. Furthermore, the interactions between Apt-receptors were found to enhance the uptake of MSNs by cancer cells. The results of in vivo studies demonstrated that the administration of MSN-DNR + CTR@CS-Apt led to a significant reduction in the expression levels of CD71 and CD235a markers, as compared to MSN-DNR + CTR@CS (p < 0.001). In conclusion, the surface modified MSNs prepared in this study showed lower IC50 against cancer cell lines and higher anticancer activity in animal models.

Evaluation of apoptotic and anti-metastatic effects by modified mesoporous silica nanoparticles (MSNs) with Zn and NH2 containing cisplatin on HT-29 cell line

Evaluation of apoptotic and anti-metastatic effects by modified mesoporous silica nanoparticles (MSNs) with Zn and NH2 containing cisplatin on HT-29 cell line

A pH-Responsive Charge-Convertible Drug Delivery Nanocarrier for Precise Starvation and Chemo Synergistic Oncotherapy.

A pH-responsive charge-convertible drug delivery nanocarrier (MSN-TPZ-GOx@ZnO@PAH-PEG-DMMA, abbreviated as MTGZ@PPD) was prepared, which could specifically release hypoxia-activated chemotherapeutic Tirapazamine (TPZ) and glucose oxidase (GOx) in the tumor site for precise starvation and chemo synergistic oncotherapy. Acid-responsive Schiff base structure modified mesoporous silica nanoparticles (MSN) co-load with GOx and TPZ, then link with ZnO quantum dots (QDs). PAH-PEG-DMMA (PPD) polymer makes MTGZ@PPD with biocompatibility and charge-convertible feature. MTGZ@PPD is negatively charged at physiological pH, and the charge reversal of PPD and acidolysis of the Schiff base structure under the acidic tumor microenvironment (TME) induce a positively charged surface, which could potentiate the cell internalization. ZnO QDs could decompose at acidic TME, achieving controllable drug release. GOx could starve the tumor cells and enhance hypoxia level, thus initiates the activation of TPZ to realize synergistic starvation therapy and chemotherapy. This intelligent MTGZ@PPD has shown great potential for starvation and chemo synergistic oncotherapy.

Organically surface engineered mesoporous silica nanoparticles control the release of quercetin by pH stimuli

Controlling the premature release of hydrophobic drugs like quercetin over physiological conditions remains a challenge motivating the development of smart and responsive drug carriers in recent years. This present work reported a surface modification of mesoporous silica nanoparticles (MSN) by a functional compound having both amines (as a positively charged group) and carboxylic (negatively charged group), namely 4-((2-aminoethyl)amino)-4-oxobut-2-enoic acid (AmEA) prepared via simple mechanochemistry approach. The impact of MSN surface modification on physical, textural, and morphological features was evaluated by TGA, N2 adsorption–desorption, PSA-zeta, SEM, and TEM. The BET surface area of AmEA-modified MSN (MSN-AmEA) was found to be 858.41 m2 g−1 with a pore size of 2.69 nm which could accommodate a high concentration of quercetin 118% higher than MSN. In addition, the colloidal stability of MSN-AmEA was greatly improved as indicated by high zeta potential especially at pH 4 compared to MSN. In contrast to MSN, MSN-AmEA has better in controlling quercetin release triggered by pH, thanks to the presence of the functional groups that have a pose-sensitive interaction hence it may fully control the quercetin release, as elaborated by the DFT study. Therefore, the controlled release of quercetin over MSN-AmEA verified its capability of acting as a smart drug delivery system.

Surface Modification of Mesoporous Silica Nanoparticles with Hexamethyl Disilazane as Smart Carriers for Tocopherol Acetate

Surface Modification of Mesoporous Silica Nanoparticles with Hexamethyl Disilazane as Smart Carriers for Tocopherol Acetate

Evaluating biological activity of folic acid-modified and 10-hydroxycamptothecin-loaded mesoporous silica nanoparticles

Targeted nanocarrier can selectively deliver anti-tumor drugs to cancer sites, improving drug efficiency. Accordingly, a targeted nanocarrier (MSN-FA) was synthesized based on folic acid (FA) modified mesoporous silica nanoparticles (MSNs). These were loaded with 10-hydroxycamptothecin (HCPT) to obtain the nano-drug MSN-FA@HCPT. These nanocarriers were characterized by transmission electron microscopy (TEM), zeta potential, ultraviolet–visible spectroscopy (UV–Vis), Fourier transform infrared spectroscopy (FT-IR) and thermogravimetric analysis (TGA). Notably, the nanocarriers were nearly spherical before and after loading HCPT and exhibited good dispersibility. Also, folate receptor (FR) over-expressing HeLa cells and FR deficient HepG2 cells were used to evaluate in vitro cellular uptake and cytotoxicity of MSN-FA@HCPT and MSN@HCPT. Interestingly, FA-modified nanocarriers enhanced the cytotoxicity of HCPT by improving drug targeting to tumor cells. Also, apoptotic and mitochondrial membrane potential (MMP) reducing effects of MSN-FA@HCPT were more prominent than the MSNs without FA modification. The MSN-FA-loaded HCPT reduced MMP, increased intracellular ROS and induced cell apoptosis. MSN-FA@HCPT can be excellent drug carriers with profound biomedical applications.

Mesoporous silica nanoparticles incorporated with Ir(III) complexes: From photophysics to photodynamic therapy

Organically modified mesoporous silica nanoparticles (MSNs) containing Ir complexes (Ir1, Ir2 and Ir3) were successfully synthesized. These Ir‐entrapped MCM41-COOH nanoparticles have shown relevant photophysical characteristics including high efficiency in the photoproduction and delivery of singlet oxygen (1O2), which is particularly promising for photodynamic therapy (PDT) applications. In vitro tests have evidenced that complex@MCM41-COOH are able to reduce cell proliferation after 10 min of blue‐light irradiation in Hep-G2 liver cancer cells.

TANNylation of mesoporous silica nanoparticles and bioactivity profiling in intestinal cells

Tannic acid (TA) is a hydrophilic polyphenol belonging to the family of tannins. Due to the presence of several functional hydroxyl groups, tannic acid is prone to interactions with cell structures, especially surface enzymes or receptor proteins. Here, different TANNylation methods were developed for the modification of mesoporous silica nanoparticles (MSNs) in order to investigate the impact of this surface functionality on the performance/biocompatibility of these nanocarriers. For the particle modification, a tannic acid silane linking-ligand was designed and subsequently installed on the MSN surface using post-grafting procedures. Grafting efficacy as well as the structural and physicochemical characteristics of the resulting particles were assessed. Then, two intestinal cell lines, HT29 and HCEC-1CT, were used for activity profiling, benchmarking the effect on the cytotoxic potential and endoplasmic reticulum (ER) stress response. The structure-activity relationships demonstrated that, in addition to the tannic acid itself, the different chemical linkers used for the binding of the polyphenol play an essential role in driving the biological response of intestinal cells. For equivalent TA concentrations, the type of coupling method not only strongly influences the grafting efficiency, but significantly alters the resulting ER response as well. The results underline that TANNylation is a promising method for enhancing cellular interactions with MSNs, although an adequate linking chemistry has to be implemented.

Friction-induced supramolecular nanovalves for the potential treatment of osteoarthritis

Owing to the overuse of rough articular cartilage, it increases the friction of joint and further leads to inflammation in joint cavities. However, the pathological changes also bring a new opportunity to achieve the treatment of osteoarthritis (OA). The increasing friction from damaged articular cartilage can convert more mechanical energy to heat. The higher localized temperature can reduce supramolecular interactions in general. Therefore, friction becomes another new activation to operate nanovalve systems for the targeting treatment of OA. Here, we designed and prepared a friction-induced nanovalve system constructed with β-cyclodextrins (β-CD)-modified mesoporous silica nanoparticles (MSN). Besides, a copolymer containing two components – guest molecules (adamantane, AD) and poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) – has been self-assembled on the surface of β-CD-modified MSN (MSN-CD) by supramolecular host–guest interactions. In this design, the charged PMPC on the MSN surface can form a dense hydration layer by ion–dipole interactions, switch the friction from surfaces to water molecules to achieve hydration lubrication, and sharply reduce the coefficient of friction (COF). Besides, the higher localized temperature from the mechanical conversion can weaken the supramolecular host–guest interactions and turn on the nanovalves to accomplish the targeted release near rough articular cartilage of OA. Even when PMPC is peeled off, the hydrophilic surface of β-CD on MSN surface can still perform the acceptable lubricating properties. The following testings of cytotoxicity by CCK-8 and live/dead staining indicated the excellent biocompatibility. Further analysis of protein expression levels has also shown the potential application in OA.

Bubble-based propulsion of engineered particles for drug delivery and immunotherapy

Biological barriers, such as mucus and cellular endothelia, obstruct the transport of drugs to diseased tissues. In this talk, I will highlight our recent work to overcome these barriers using engineering particles that undergo bubble-based propulsion in response to ultrasound. I will focus on two innovations. First, I will share our collaborative effort to synthesize hydrophobically modified mesoporous silica nanoparticles (MSNs) stabilized with phospholipids that entrap hydrophobic drugs. When insonated with high-intensity focused ultrasound, the MSNs undergo cavitation to rapidly propel through dense media and release drugs. Second, I will share our effort to fabricate microparticles with arbitrary three-dimensional shapes using two-photon lithography. These microparticles are capable of entrapping air bubbles of a defined size, leading to their efficient, frequency-dependent propulsion when stimulated by ultrasound. By modifying the surfaces of these particles, they can robustly attach to epithelial cell layers and release small molecule drugs for extended durations. By way of outlook, I will discuss how these technologies have potential to stimulate immune cells against tumor progression and to abate inflammation in auto-immune diseases.

A pH-responsive mesoporous silica nanoparticles-based drug delivery system with controlled release of andrographolide for OA treatment.

Andrographolide (AG) has favorable anti-inflammatory and antioxidative capacity. However, it has low bioavailability due to high lipophilicity and can be easily cleared by the synovial fluid after intra-articular injection, leading to low therapeutic efficiency in osteoarthritis (OA). Herein, we designed a nano-sized pH-responsive drug delivery system (DDS) for OA treatment by using modified mesoporous silica nanoparticles (MSNs) with pH-responsive polyacrylic acid (PAA) for loading of AG to form AG@MSNs-PAA nanoplatform. The nanoparticles have uniform size (∼120 nm), high drug loading efficiency (22.38 ± 0.71%) and pH-responsive properties, beneficial to sustained release in OA environment. Compared with AG, AG@MSNs-PAA showed enhanced antiarthritic efficacy and chondro-protective capacity based on IL-1β-stimulated chondrocytes and anterior cruciate ligament transection-induced rat OA model, as demonstrated by lower expression of inflammatory factors and better prevention of proteoglycan loss. Therefore, the AG@MSNs-PAA nanoplatform may be developed as a promising OA-specific and on-demand DDS.

Direct surface modification of mesoporous silica nanoparticles by DBD plasma as a green approach to prepare dual-responsive drug delivery system

This paper deals with uniformly surface modification of mesoporous silica nanoparticles by applying dielectric barrier discharge (DBD) plasma as an energy-efficient and green approach. First, the mesoporous silica nanoparticles were synthesized from rice husk (RMSN-D) as an economic and biocompatible natural source. The surface modification stage by DBD plasma was performed in two methods: i) Direct mode and ii) Direct hybrid mode. The structure and physicochemical properties of the nanoparticles were characterized by XRD, FT-IR, Fe-SEM/EDS, TEM, EDS, BET, and HNMR techniques. Doxorubicin (Dox) was exploited as a model drug, and in-vitro Dox release was investigated. The biocompatibility of nanocarriers was accepted by MTT test on HFF-2 cell line as a normal modal cell. For the advanced cellular study, apoptosis of the MCF-7 cell line treated with Dox-loaded nanocarriers was investigated by flow cytometric analysis and morphological study by fluorescent microscopy. The results showed that Dox-loaded RMSN-D modified by direct hybrid mode induced a high level of apoptosis in the MCF-7 cells.

Evaluation of Chitosan Derivatives Modified Mesoporous Silica Nanoparticles as Delivery Carrier

Chitosan is a non-toxic biological material, but chitosan is insoluble in water, which hinders the development and utilization of chitosan. Chitosan derivatives N-2-Hydroxypropyl trimethyl ammonium chloride (N-2-HACC) and carboxymethyl chitosan (CMCS) with good water solubility were synthesized by our laboratory. In this study, we synthesized mesoporous SiO2 nanoparticles by the emulsion, and then the mesoporous SiO2 nanoparticles were modified with γ-aminopropyltriethoxysilane to synthesize aminated mesoporous SiO2 nanoparticles; CMCS and N-2-HACC was used to cross-link the aminated mesoporous SiO2 nanoparticles to construct SiO2@CMCS-N-2-HACC nanoparticles. Because the aminated mesoporous SiO2 nanoparticles with positively charged can react with the mucous membranes, the virus enters the body mainly through mucous membranes, so Newcastle disease virus (NDV) was selected as the model drug to evaluate the performance of the SiO2@CMCS-N-2-HACC nanoparticles. We prepared the SiO2@CMCS-N-2-HACC nanoparticles loaded with inactivated NDV (NDV/SiO2@CMCS-N-2-HACC). The SiO2@CMCS-N-2-HACC nanoparticles as delivery carrier had high loading capacity, low cytotoxicity, good acid resistance and bile resistance and enteric solubility, and the structure of NDV protein encapsulated in the nano vaccine was not destroyed. In addition, the SiO2@CMCS-N-2-HACC nanoparticles could sustain slowly released NDV. Therefore, the SiO2@CMCS-N-2-HACC nanoparticles have the potential to be served as delivery vehicle for vaccine and/or drug.

Benzene-Bridged Organosilica Modified Mesoporous Silica Nanoparticles via an Acid-Catalysis Approach.

Surface functionalization of mesoporous silica nanoparticles is important for their applications but fairly challenging using benzene-bridged organosilane as the precursor through the postsynthesis approach. Herein, we report an acid-catalysis approach for the postmodification of benzene-bridged organosilica onto the surface of large-pore mesoporous silica nanoparticles. By using HCl (∼1 M) as the acid catalyst in a tetrahydrofuran solvent, the self-assembly of the bridged organosilica precursor is avoided, while surface modification of mesoporous silica nanoparticles is promoted with controllable organic contents and retained large pore sizes. This strategy can also be applied to the postmodification of organosilica with end benzene groups. The strategy developed in this study is expected to be applied for the postmodification of other organosilica precursors with various functions.

Fabrication of a pH-Responsive 5-FU@MSN-SA Nanoplatform for Anti-Tumor Activity

Design of high-performance drug delivery system is necessary to improve the anticancer ability of 5-fluorouracil (5-FU). In this work, we developed a pH-responsive 5-FU loaded and sodium alginate (SA) modified mesoporous silica nanoparticles (MSNs) drug delivery system (5-FU@MSN-SA). After 5-FU was loaded into the pores, MSNs were successfully functionalized with amino groups and then capped by sodium alginate. Compared to acidic conditions, the drug release rate in the neutral environment was quite low. Moreover, detailed investigations confirmed that 5-FU@MSN-SA can easily be up-taken by cancer cells and proved the high cytotoxicity to 4T1 cells. The calculated IC[Formula: see text] values for 5-FU and 5-FU@MSN-SA were 34.67[Formula: see text][Formula: see text][Formula: see text]g/mL and 54.95[Formula: see text][Formula: see text][Formula: see text]g/mL, respectively. These results indicated that 5-FU@MSNs-SA can be a promising nanoplatform in cancer therapy.

Zinc-doped silica/polyaniline core/shell nanoparticles towards corrosion protection epoxy nanocomposite coatings

Commercial paints and coatings can serve as a protective barrier for metallic substrates in a corrosive environment. A considerable variety of nanostructures can be embedded in a polymeric coating to achieve both barrier and active protection. This research aims to elucidate the role of polyaniline (PANI) as an active polyelectrolyte modifier for the surface modification of mesoporous silica nanoparticles (MSNs) doped with zinc cations (Zn2+). To characterize the samples, we employed different techniques, including field-emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), N2 adsorption-desorption, Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy, X-ray diffraction (XRD), thermogravimetric analysis (TGA), inductively coupled plasma optical emission spectroscopy (ICP-OES), rheometric mechanical spectroscopy (RMS), differential scanning calorimetry (DSC), tensile, and electrochemical impedance spectroscopy (EIS). Characterization of PANI-MSNs proved the formation of PANI shells onto the surface of silica cores, and pH triggered the release of Zn2+ at the alkaline condition. Enhancement in rheological, thermal, and mechanical characteristics revealed good dispersion and chemical interaction between PANI coated nanoparticles and the epoxy matrix. Moreover, epoxy nanocomposite coatings illustrated a dual barrier/active protection after 50 days of salt immersion.