Use Of Mesoporous Silica Nanoparticles Research Articles

Dynamic light scattering unveils stochastic degradation in large-pore mesoporous silica nanoparticles

Mesoporous Silica Nanoparticles (MSNs) have been increasingly investigated as versatile drug delivery carriers. A particular challenge for the systemic use of MSNs lies in the control of their degradation, which has not been fully understood until now. We implemented standard dynamic light scattering (DLS) experiments and introduced a novel DLS technique in a confocal volume to track the dynamics of large-pore MSN degradation in situ. This unique DLS technique, which involves a small observation volume, was chosen for its ability to count particle by particle during the degradation process, a method that has not been commonly used in nanoparticle research. The experiments were performed in different media compositions at low particle concentrations, below the silica solubility limit. MSNs with large conical pores were prepared and studied as they offer the possibility to incorporate and release large-sized biomolecules. Large-pore MSNs followed a singular degradation mechanism following a stochastic-like behavior, a finding that challenges the common idea that all nanoparticles (NPs) degrade similarly and homogeneously over time. We showed that some NPs are observed intact over a prolonged period while most other NPs have already vanished or been transformed into swollen NPs. Thus, a heterogeneous degradation process occurs, while the total concentration of NPs undergoes an exponential decay. These large conical pores MSNs will be utilized as reliable biomolecule nanocarriers by predicting the factors underlying the NP hydrolytic stability.

Mesoporous Silica Nanoparticles as an Ideal Platform for Cancer Immunotherapy: Recent Advances and Future Directions.

Cancer immunotherapy recently transforms the traditional approaches against various cancer malignancies. Immunotherapy includes systemic and local treatments to enhance immune responses against cancer and involves strategies such as immune checkpoints, cancer vaccines, immune modulatory agents, mimetic antigen-presenting cells, and adoptive cell therapy. Despite promising results, these approaches still suffer from several limitations including lack of precise delivery of immune-modulatory agents to the target cells and off-target toxicity, among others, that can be overcome using nanotechnology. Mesoporous silica nanoparticles (MSNs) are investigated to improve various aspects of cancer immunotherapy attributed to the advantageous structural features of this nanomaterial. MSNs can be engineered to alter their properties such as size, shape, porosity, surface functionality, and adjuvanticity. This review explores the immunological properties of MSNs and the use of MSNs as delivery vehicles for immune-adjuvants, vaccines, and mimetic antigen-presenting cells (APCs). The review also details the current strategies to remodel the tumor microenvironment to positively reciprocate toward the anti-tumor immune cells and the use of MSNs for immunotherapy in combination with other anti-tumor therapies including photodynamic/thermal therapies to enhance the therapeutic effect against cancer. Last, the present demands and future scenarios for the use of MSNs for cancer immunotherapy are discussed.

Bioinspired extracellular vesicle-coated silica nanoparticles as selective delivery systems

In recent years, there has been a breakthrough in the integration of artificial nanoplatforms with natural biomaterials for the development of more efficient drug delivery systems. The formulation of bioinspired nanosystems, combining the benefits of synthetic nanoparticles with the natural features of biological materials, provides an efficient strategy to improve nanoparticle circulation time, biocompatibility and specificity toward targeted tissues. Among others biological materials, extracellular vesicles (EVs), membranous structures secreted by many types of cells composed by a protein rich lipid bilayer, have shown a great potential as drug delivery systems themselves and in combination with artificial nanoparticles. The reason for such interest relays on their natural properties, such as overcoming several biological barriers or migration towards specific tissues. Here, we propose the use of mesoporous silica nanoparticles (MSNs) as efficient and versatile nanocarriers in combination with tumor derived extracellular vesicles (EVs) for the development of selective drug delivery systems. The hybrid nanosystems demonstrated selective cellular internalization in parent cells, indicating that the EV targeting capabilities were efficiently transferred to MSNs by the developed coating strategy. As a result, EVs-coated MSNs provided an enhanced and selective intracellular accumulation of doxorubicin and a specific cytotoxic activity against targeted cancer cells, revealing these hybrid nanosystems as promising candidates for the development of targeted treatments.

Enhancing Light Harvesting in Dye-Sensitized Solar Cells through Mesoporous Silica Nanoparticle-Mediated Diffuse Scattering Back Reflectors

Dye-sensitized solar cells (DSSCs) hold unique promise in solar photovoltaics owing to their low-cost fabrication and high efficiency in ambient conditions. However, to improve their commercial viability, effective, and low-cost methods must be employed to enhance their light harvesting capabilities, and hence photovoltaic (PV) performance. Improving the absorption of incoming light is a critical strategy for maximizing solar cell efficiency while overcoming material limitations. Mesoporous silica nanoparticles (MSNs) were employed herein as a reflective layer on the back of transparent counter electrodes. Chemically synthesized MSNs were applied to DSSCs via bar coating as a facile fabrication step compatible with roll-to-roll manufacturing. The MSNs diffusely scatter the unused incident light transmitted through the DSSCs back into the photoactive layers, increasing the absorption of light by N719 dye molecules. This resulted in a 20% increase in power conversion efficiency (PCE), from 5.57% in a standard cell to 6.68% with the addition of MSNs. The improved performance is attributed to an increase in photon absorption which led to the generation of a higher number of charge carriers, thus increasing the current density in DSSCs. These results were corroborated with electrochemical impedance spectroscopy (EIS), which showed improved charge transport kinetics. The use of MSNs as reflectors proved to be an effective practical method for enhancing the performance of thin film solar cells. Due to silica’s abundance and biocompatibility, MSNs are an attractive material for meeting the low-cost and non-toxic requirements for commercially viable integrated PVs.

Mesoporous Silica Nanoparticles as a Gene Delivery Platform for Cancer Therapy.

Cancer remains a major global health challenge. Traditional chemotherapy often results in side effects and drug resistance, necessitating the development of alternative treatment strategies such as gene therapy. Mesoporous silica nanoparticles (MSNs) offer many advantages as a gene delivery carrier, including high loading capacity, controlled drug release, and easy surface functionalization. MSNs are biodegradable and biocompatible, making them promising candidates for drug delivery applications. Recent studies demonstrating the use of MSNs for the delivery of therapeutic nucleic acids to cancer cells have been reviewed, along with their potential as a tool for cancer therapy. The major challenges and future interventions of MSNs as gene delivery carriers for cancer therapy are discussed.

Mesoporous Silica Nanoparticles as a Potential Nanoplatform: Therapeutic Applications and Considerations.

With advances in nanotechnology, nanoparticles have come to be regarded as carriers of therapeutic agents and have been widely studied to overcome various diseases in the biomedical field. Among these particles, mesoporous silica nanoparticles (MSNs) have been investigated as potential nanocarriers to deliver drug molecules to various target sites in the body. This review introduces the physicochemical properties of MSNs and synthesis procedures of MSN-based nanoplatforms. Moreover, we focus on updating biomedical applications of MSNs as a carrier of therapeutic or diagnostic cargo and review clinical trials using silica-nanoparticle-based systems. Herein, on the one hand, we pay attention to the pharmaceutical advantages of MSNs, including nanometer particle size, high surface area, and porous structures, thus enabling efficient delivery of high drug-loading content. On the other hand, we look through biosafety and toxicity issues associated with MSN-based platforms. Based on many reports so far, MSNs have been widely applied to construct tissue engineering platforms as well as treat various diseases, including cancer, by surface functionalization or incorporation of stimuli-responsive components. However, even with the advantageous aspects that MSNs possess, there are still considerations, such as optimizing physicochemical properties or dosage regimens, regarding use of MSNs in clinics. Progress in synthesis procedures and scale-up production as well as a thorough investigation into the biosafety of MSNs would enable design of innovative and safe MSN-based platforms in biomedical fields.

Lycopene, Mesoporous Silica Nanoparticles and Their Association: A Possible Alternative against Vulvovaginal Candidiasis?

Commonly found colonizing the human microbiota, Candida albicans is a microorganism known for its ability to cause infections, mainly in the vulvovaginal region known as vulvovaginal candidiasis (VVC). This pathology is, in fact, one of the main C. albicans clinical manifestations, changing from a colonizer to a pathogen. The increase in VVC cases and limited antifungal therapy make C. albicans an increasingly frequent risk in women's lives, especially in immunocompromised patients, pregnant women and the elderly. Therefore, it is necessary to develop new therapeutic options, especially those involving natural products associated with nanotechnology, such as lycopene and mesoporous silica nanoparticles. From this perspective, this study sought to assess whether lycopene, mesoporous silica nanoparticles and their combination would be an attractive product for the treatment of this serious disease through microbiological in vitro tests and acute toxicity tests in an alternative in vivo model of Galleria mellonella. Although they did not show desirable antifungal activity for VVC therapy, the present study strongly encourages the use of mesoporous silica nanoparticles impregnated with lycopene for the treatment of other human pathologies, since the products evaluated here did not show toxicity in the in vivo test performed, being therefore, a topic to be further explored.

Key Parameters for the Rational Design, Synthesis, and Functionalization of Biocompatible Mesoporous Silica Nanoparticles.

Over the last few years, research on silica nanoparticles has rapidly increased. Particularly on mesoporous silica nanoparticles (MSNs), as nanocarriers for the treatment of various diseases because of their physicochemical properties and biocompatibility. The use of MSNs combined with therapeutic agents can provide better encapsulation and effective delivery. MSNs as nanocarriers might also be a promising tool to lower the therapeutic dosage levels and thereby to reduce undesired side effects. Researchers have explored several routes to conjugate both imaging and therapeutic agents onto MSNs, thus expanding their potential as theranostic platforms, in order to allow for the early diagnosis and treatment of diseases. This review introduces a general overview of recent advances in the field of silica nanoparticles. In particular, the review tackles the fundamental aspects of silicate materials, including a historical presentation to new silicates and then focusing on the key parameters that govern the tailored synthesis of functional MSNs. Finally, the biomedical applications of MSNs are briefly revised, along with their biocompatibility, biodistribution and degradation. This review aims to provide the reader with the tools for a rational design of biocompatible MSNs for their application in the biomedical field. Particular attention is paid to the role that the synthesis conditions have on the physicochemical properties of the resulting MSNs, which, in turn, will determine their pharmacological behavior. Several recent examples are highlighted to stress the potential that MSNs hold as drug delivery systems, for biomedical imaging, as vaccine adjuvants and as theragnostic agents.

Development of Proanthocyanidin-Loaded Mesoporous Silica Nanoparticles for Improving Dental Adhesion.

Dentin biomodification is a promising approach to enhance dental tissue biomechanics and biostability for restorative and reparative therapies. One of the most active dentin tissue biomodifiers is proanthocyanidin (PAC)-rich natural extracts, which are used in the dental bonding procedure in combination with resin-based adhesives (RBAs). This study aimed to investigate the use of mesoporous silica nanoparticles (MSNs) for the sustained delivery of PACs for dentin biomodification as a novel drug-delivery system for dental applications. The effects of the incorporation of MSN functionalized with 3-aminopropyltriethoxysilane (APTES) and loaded with PAC into an experimental RBA were assessed by characterizing the material mechanical properties. In addition, the immediate and long-term bonding performance of an experimental resin-based primer (RBP) containing MSN-APTES loaded with PAC was also evaluated. For that, different formulations of RBA and RBP were prepared containing 20% w/v MSN-APTES loaded with PAC before or after functionalization (MSN-PAC-APTES and MSN-APTES-PAC, respectively). The incorporation of MSN-APTES-PAC did not negatively impact the degree of conversion or the overall mechanical properties of the RBA. However, adding MSN-PAC-APTES resulted in inferior mechanical properties of the experimental RBA. In the adhesion studies, APTES-functionalized MSN was successfully added to an experimental RBP for drug-delivery purposes without compromising the bond strength to the dentin or the failure mode. Interestingly, the sequence of surface functionalization with APTES resulted in differences in the bonding performance, with better long-term results for RBP containing MSN loaded with PAC after functionalization.

Nanoparticle combination for precise stroma modulation and improved delivery for pancreatic cancer.

Therapeutic success in the treatment of pancreatic ductal adenocarcinoma (PDAC) is hindered by the extensive stroma associated to this disease. Stroma is composed of cellular and non-cellular components supporting and evolving with the tumor. One of the most studied mediators of cancer cell-stroma crosstalk is sonic hedgehog (SHh) pathway leading to the intense desmoplasia observed in PDAC tumors. Herein, we demonstrate that the use of mesoporous silica nanoparticles (MSNs) containing an SHh inhibitor, cyclopamine (CyP), and the combination of chemotherapeutic drugs (Gemcitabine (Gem)/cisplatin (cisPt)) as the main delivery system for the sequential treatment led to the reduction in tumor stroma along with an improvement in the treatment of PDAC. We synthesized two versions of the MSN-based platform containing the SHh inhibitor (CyP-MSNs) and the drug combination (PEG-Gem-cisPt-MSNs). In vitro and in vivo protein analysis show that CyP-MSNs effectively inhibited the SHh pathway. In addition, the sequential combination of CyP-MSNs followed by PEG-Gem-cisPt-MSNs led to effective stromal modulation, increased access of secondary PEG-Gem-cisPt-MSNs at the tumor site, and improved therapeutic performance in HPAF II xenograft mice. Taken together, our findings support the potential of drug delivery using MSNs for stroma modulation and to prevent pancreatic cancer progression.

Mesoporous Silica Nanoparticle-Based Drug Delivery Systems for the Treatment of Pancreatic Cancer: A Systematic Literature Overview.

Pancreatic cancer is a devastating disease with the worst outcome of any human cancer. Despite significant improvements in cancer treatment in general, little progress has been made in pancreatic cancer (PDAC), resulting in an overall 5-year survival rate of less than 10%. This dismal prognosis can be attributed to the limited clinical efficacy of systemic chemotherapy due to its high toxicity and consequent dose reductions. Targeted delivery of chemotherapeutic drugs to PDAC cells without affecting healthy non-tumor cells will largely reduce collateral toxicity leading to reduced morbidity and an increased number of PDAC patients eligible for chemotherapy treatment. To achieve targeted delivery in PDAC, several strategies have been explored over the last years, and especially the use of mesoporous silica nanoparticles (MSNs) seem an attractive approach. MSNs show high biocompatibility, are relatively easy to surface modify, and the porous structure of MSNs enables high drug-loading capacity. In the current systematic review, we explore the suitability of MSN-based targeted therapies in the setting of PDAC. We provide an extensive overview of MSN-formulations employed in preclinical PDAC models and conclude that MSN-based tumor-targeting strategies may indeed hold therapeutic potential for PDAC, although true clinical translation has lagged behind.

Nanoantibiotics Based in Mesoporous Silica Nanoparticles: New Formulations for Bacterial Infection Treatment.

This review focuses on the design of mesoporous silica nanoparticles for infection treatment. Written within a general context of contributions in the field, this manuscript highlights the major scientific achievements accomplished by professor Vallet-Regí’s research group in the field of silica-based mesoporous materials for drug delivery. The aim is to bring out her pivotal role on the envisage of a new era of nanoantibiotics by using a deep knowledge on mesoporous materials as drug delivery systems and by applying cutting-edge technologies to design and engineer advanced nanoweapons to fight infection. This review has been divided in two main sections: the first part overviews the influence of the textural and chemical properties of silica-based mesoporous materials on the loading and release of antibiotic molecules, depending on the host–guest interactions. Furthermore, this section also remarks on the potential of molecular modelling in the design and comprehension of the performance of these release systems. The second part describes the more recent advances in the use of mesoporous silica nanoparticles as versatile nanoplatforms for the development of novel targeted and stimuli-responsive antimicrobial nanoformulations for future application in personalized infection therapies.

Preparation and evaluation of mesoporous silica nanoparticles loaded quercetin against bacterial infections in Oreochromis niloticus

The present work investigated the potential use of mesoporous silica nanoparticles (MSN) to deliver quercetin in fish through oral route to protect the fish from infection caused by S. agalactiae and K. pneumoniae. The MSNs were synthesized by sol gel method. Polyethylene glycol (PEG)-coated MSNs (PMSNs) were synthesized employing a similar procedure by the addition of PEG and Quercetin conjugated PMSNs (QMSNs) were prepared by the co-precipitation process. These nanoparticles were characterized by UV–vis spectrum, FTIR, XRD, DLS and Zeta potential. The morphology and particle size measurements of the nanoparticles were studied by FE-SEM. The in vitro drug release profile was assessed at different pH, and pH 6.5 was found to be more efficient to release quercetin. The cytotoxicity of QMSNs nanoparticles was evaluated by MTT assay using tilapia gill (TG) cell line. The expression of immune related gene in gill, brain and liver were found to be increased significantly in fish (Oreochromis niloticus) fed with experimental feed when compared to the control fish fed with normal feed. The antibacterial effect of QMSNs against S. agalactiae and K. pneumoniae infection were analysed. The QMSNs produced strong antibacterial activity aganist both the pathogens. The results of this study indicate that quercetin can be easily delivered into fish by feeding with QMSNs for treatment against bacterial infections.

Recent Advances in the Use of Mesoporous Silica Nanoparticles for the Diagnosis of Bacterial Infections.

Public awareness of infectious diseases has increased in recent months, not only due to the current COVID-19 outbreak but also because of antimicrobial resistance (AMR) being declared a top-10 global health threat by the World Health Organization (WHO) in 2019. These global issues have spiked the realization that new and more efficient methods and approaches are urgently required to efficiently combat and overcome the failures in the diagnosis and therapy of infectious disease. This holds true not only for current diseases, but we should also have enough readiness to fight the unforeseen diseases so as to avoid future pandemics. A paradigm shift is needed, not only in infection treatment, but also diagnostic practices, to overcome the potential failures associated with early diagnosis stages, leading to unnecessary and inefficient treatments, while simultaneously promoting AMR. With the development of nanotechnology, nanomaterials fabricated as multifunctional nano-platforms for antibacterial therapeutics, diagnostics, or both (known as “theranostics”) have attracted increasing attention. In the research field of nanomedicine, mesoporous silica nanoparticles (MSN) with a tailored structure, large surface area, high loading capacity, abundant chemical versatility, and acceptable biocompatibility, have shown great potential to integrate the desired functions for diagnosis of bacterial infections. The focus of this review is to present the advances in mesoporous materials in the form of nanoparticles (NPs) or composites that can easily and flexibly accommodate dual or multifunctional capabilities of separation, identification and tracking performed during the diagnosis of infectious diseases together with the inspiring NP designs in diagnosis of bacterial infections.

Mesoporous Silica Nanoparticles Improve Oral Delivery of Antitubercular Bicyclic Nitroimidazoles.

Pretomanid and MCC7433, a novel nitroimidazopyrazinone analog, are promising antitubercular agents that belong to the bicyclic nitroimidazole family. Despite possessing high cell permeability, they suffer from poor aqueous solubility and require specialized formulations in order to be orally bioavailable. To address this limitation, we investigated the use of mesoporous silica nanoparticles (MCM-41) as drug carriers. MCM-41 nanoparticles were synthesized using a sol–gel method, and their surface was further modified with amine and phosphonate groups. A simple rotary evaporation method was used to incorporate the compounds of interest into the nanoparticles, leading to a high encapsulation efficiency of ≥86% with ∼10% loading (w/w). An overall significant improvement of solubility was also observed, and the pharmacological activity of pretomanid and MCC7433 was fully retained when tested in vitro against Mycobacterium tuberculosis using these nanocarriers. Amino-functionalized MCM-41 nanoparticles were found to enhance the systemic exposure of MCC7433 in mice (1.3-fold higher Cmax) compared to MCC7433 alone. The current work highlights the potential of using nanoparticles such as mesoporous silica as a carrier for oral delivery of poorly soluble antibacterial agents against tuberculosis.

Recent Advances Toward the Use of Mesoporous Silica Nanoparticles for the Treatment of Bacterial Infections.

It is a fact that the use of antibiotics is inducing a growing resistance on bacteria. This situation is not only the consequence of a drugs’ misuse, but a direct consequence of a widespread and continuous use. Current studies suggest that this effect could be reversed by using abandoned antibiotics to which bacteria have lost their resistance, but this is only a temporary solution that in near future would lead to new resistance problems. Fortunately, current nanotechnology offers a new life for old and new antibiotics, which could have significantly different pharmacokinetics when properly delivered; enabling new routes able to bypass acquired resistances. In this contribution, we will focus on the use of porous silica nanoparticles as functional carriers for the delivery of antibiotics and biocides in combination with additional features like membrane sensitizing and heavy metal-driven metabolic-disrupting therapies as two of the most interesting combination therapies.

Mesoporous Silica Nanoparticles as Carriers for Biomolecules in Cancer Therapy.

Mesoporous silica nanoparticles (MSNs) offer many advantageous properties for applications in the field of nanobiotechnology. Loading of small molecules into MSNs is straightforward and widely applied, but with the upswing of both research and commercial interest in biological drugs in recent years, also biomacromolecules have been loaded into MSNsfor delivery purposes. MSNs possess many critical properties making them a promising and versatile carrier for biomacromolecular delivery. In this chapter, we review the effects of the various structural parameters of MSNs on the effective loading of biomacromolecular therapeutics, with focus on maintaining stability and drug delivery performance. We also emphasize recent studies involving the use of MSNs in the delivery of biomacromolecular drugs, especially for cancer treatment.

Low-angle X-ray scattering for the determination of the size of mesoporous silica nanoparticles

In the last two decades, Mesoporous Silica Nanoparticles (MSNs) were given a substantial interest due to their unique properties and wide range of applications. The size is a key feature which determines the use of MSNs. Transmission Electron Microscopy (TEM) is a standard technique for MSNs’ size determination. Despite reliable, yet it has some drawbacks, being time consuming, destructive and requires complex sample preparation. Therefore, this work aims at introducing Low-angle X-ray Scattering (LAXS) as a time-saving, non-destructive and inexpensive tool for the determination of the size of MSNs. Different sizes of MSNs are prepared using different concentrations of ammonium hydroxide (catalyst) and their corresponding LAXS profiles are recorded. LAXS profile parameters (peak position and area under peak) are found to exhibit a strong linear dependence on the size of MSNs determined using the standard TEM technique. Moreover, the pore sizes calculated from LAXS profiles show linear dependence on the size of MSNs. For MSNs in the range from 60 to 170 nm, two mathematical linear fitting equations are introduced for the determination of the size of MSNs by direct substitution using LAXS profile parameters. One more equation is introduced for the calculation of the size of MSNs directly from their pore size.

A short review on recent progress in mesoporous silicas for the removal of metal ions from water

Mesoporous silica nanoparticles (MSNs) are used as nanoadsorbents for the removal of pollutants from water. MSNs have shown very high adsorption efficiencies for various toxic metal ions from water. Recently, significant new advancements are noticed in this field of research with a potential to develop a water purification technology based on MSNs. In this overview, latest reports about the use of porous silica particles for the removal of metal ions from water are listed and critically analyzed. The maximum adsorption efficiencies of the newly developed porous silica-based materials for different metal ions are studied and comparatively analyzed. Recent trends show that, the majority of works are focused on development of hybrid and functional porous silica nanoparticles for the removal of Pb, Cd, Cu, and Cr metal ions from water. The collective information presented here will help to design future research strategies for the development and use of MSNs for removal of various pollutants from water.

Hydrolytic surface erosion of mesoporous silica nanoparticles for efficient intracellular delivery of cytochrome c

Delivery of apoptosis-associated proteins is an attractive approach to treat cancer, but their large molecular sizes and membrane-impermeability require the use of a suitable delivery carrier. As a versatile drug carrier, mesoporous silica nanoparticles (MSNs) have been utilized to transport a variety of therapeutic molecules. However, the use of MSNs for protein delivery has been limited because their conventionally obtainable pore size (ca. 2–3 nm in diameter) is too small to load large-sized biomolecular cargos. In this article, we present surface erosion of MSNs by hydrolytic degradation as a new strategy to obtain a mesoporous colloidal carrier for effective delivery of a bulky apoptosis-inducible protein, cytochrome c (CYT). A series of physicochemical properties of particles were analyzed before and after the hydrolytic surface erosion of pristine small-pored MSNs and the subsequent CYT loading. The results showed that hydrolytic degradation of MSNs imparts beneficial structural features for CYT loading and release, i.e., enlarged pores (up to ~10 nm in diameter) and roughened surface texture, leading to significantly enhanced intracellular delivery of CYT over conventional small-pored MSNs. The present results may offer a useful insight into silica degradability for tuning the internal/external surface characteristics of MSN-based colloidal particles to open a wide range of biomedical applications.