Virus-Shaped Mesoporous Silica Nanostars to Improve the Transport of Drugs across the Blood-Brain Barrier.

Conditions affecting the brain are the second leading cause of death globally. One of the main challenges for drugs targeting brain diseases is passing the blood-brain barrier (BBB). Here, the effectiveness of mesoporous silica nanostars (MSiNSs) with two different spike lengths to cross an in vitro BBB multicellular model was evaluated and compared to spherical nanoparticles (MSiNP). A modified sol-gel single-micelle epitaxial growth was used to produce MSiNS, which showed no cytotoxicity or immunogenicity at concentrations of up to 1 µg mL-1 in peripheral blood mononuclear and neuronal cells. The nanostar MSiNS effectively penetrated the BBB model after 24 h, and MSiNS-1 with a shorter spike length (9 ± 2 nm) crossed the in vitro BBB model more rapidly than the MSiNS-2 with longer spikes (18 ± 4 nm) or spherical MSiNP at 96 h, which accumulated in the apical and basolateral sides, respectively. Molecular dynamic simulations illustrated an increase in configurational flexibility of the lipid bilayer during contact with the MSiNS, resulting in wrapping, whereas the MSiNP suppressed membrane fluctuations. This work advances an effective brain drug delivery system based on virus-like shaped MSiNS for the treatment of different brain diseases and a mechanism for their interaction with lipid bilayers.

Induction of antigen-specific immunity by mesoporous silica nanoparticles incorporating antigen peptides.

Mesoporous silica nanoparticles (MSNs) are physically and chemically stable inorganic nanomaterials that have been attracting much attention as carriers for drug delivery systems in the field of nanomedicine. In the present study, we investigated the potential of MSN vaccines that incorporate antigen peptides for use in cancer immunotherapy. In vitro experiments demonstrated that fluorescently labeled MSNs accumulated in a line of mouse dendritic cells (DC2.4 cells), where the particles localized to the cytosol. These observations could suggest that MSNs have potential for use in delivering the loaded molecules into antigen-presenting cells, thereby stimulating the host acquired immune system. In vivo experiments demonstrated prolonged survival in mice implanted with ovalbumin (OVA)-expressing lymphoma cells (E.G7-OVA cells) following subcutaneous inoculation with MSNs incorporating OVA antigen peptides. Furthermore, OVA-specific immunoglobulin G antibodies and cytotoxic T lymphocytes were detected in the serum and the spleen cells, respectively, of mice inoculated with an MSN-OVA vaccine, indicating the induction of antigen-specific responses in both the humoral and cellular immune systems. These results suggested that the MSN therapies incorporating antigen peptides may serve as novel vaccines for cancer immunotherapy.

A Biodegradable Nano-Drug Delivery Platform for Co-Delivery of Minocycline and Chitosan to Achieve Efficient and Safe Non-Surgical Periodontitis Therapy.

INTRODUCTION: Mesoporous silica nanoparticles (MSN) are widely used as ideal nanovehicles for the delivery of chemotherapeutic drugs. However, the balance between high anti-periodontitis activity and low biotoxicity has been challenging to maintain in most relevant studies owing to the slow degradation of silica in living organisms. METHOD: In this study, -responsive hydroxyapatite (HAP) was doped into the MSN skeleton, and the chemotherapeutic drug minocycline hydrochloride (MH) was loaded into the pores of MSN, forming a negatively charged drug delivery system. Cationic chitosan (COS) is a biodegradable material with high antibacterial performance and good biosafety. In this study, COS was immobilized on the surface of the drug-loaded particles through stable charge interaction to construct a composite drug delivery system (MH@MSNion@COS). RESULTS: In vitro and cellular experiments demonstrated effective degradation of the nanocarrier system and synchronized controlled release of the drug. Notably, compared with single MH administration, this system, in which MH and COS jointly regulated the expression levels of periodontitis- associated inflammatory factors (TNF-α, IL-6, IL-1ß, and iNOS), better inhibited the progress of periodontitis and induced tissue regeneration without showing significant toxic side effects in cells. CONCLUSION: This system provides a promising strategy for the design of intelligent, efficient, and safe anti-periodontitis drug delivery systems.

GSH-responsive degradable nanodrug for glucose metabolism intervention and induction of ferroptosis to enhance magnetothermal anti-tumor therapy.

The challenges associated with activating ferroptosis for cancer therapy primarily arise from obstacles related to redox and iron homeostasis, which hinder the susceptibility of tumor cells to ferroptosis. However, the specific mechanisms of ferroptosis resistance, especially those intertwined with abnormal metabolic processes within tumor cells, have been consistently underestimated. In response, we present an innovative glutathione-responsive magnetocaloric therapy nanodrug termed LFMP. LFMP consists of lonidamine (LND) loaded into PEG-modified magnetic nanoparticles with a Fe3O4 core and coated with disulfide bonds-bridged mesoporous silica shells. This nanodrug is designed to induce an accelerated ferroptosis-activating state in tumor cells by disrupting homeostasis. Under the dual effects of alternating magnetic fields and high concentrations of glutathione in the tumor microenvironment, LFMP undergoes disintegration, releasing drugs. LND intervenes in cell metabolism by inhibiting glycolysis, ultimately enhancing iron death and leading to synthetic glutathione consumption. The disulfide bonds play a pivotal role in disrupting intracellular redox homeostasis by depleting glutathione and inactivating glutathione peroxidase 4 (GPX4), synergizing with LND to enhance the sensitivity of tumor cells to ferroptosis. This process intensifies oxidative stress, further impairing redox homeostasis. Furthermore, LFMP exacerbates mitochondrial dysfunction, triggering ROS formation and lactate buildup in cancer cells, resulting in increased acidity and subsequent tumor cell death. Importantly, LFMP significantly suppresses tumor cell proliferation with minimal side effects both in vitro and in vivo, exhibiting satisfactory T2-weighted MR imaging properties. In conclusion, this magnetic hyperthermia-based nanomedicine strategy presents a promising and innovative approach for antitumor therapy.

A novel FK506-loading mesoporous silica nanoparticle homing to lymph nodes for transplant rejection treatment.

Tacrolimus (FK506) is an effective therapeutic for transplant rejection in clinical practice, primarily inhibiting rejection by suppressing the activation and proliferation of allogeneic T cells in the lymph nodes (LNs). However, conventional administration methods face challenges in directly delivering free FK506 to the LNs. In this study, we introduce a novel LN-targeted delivery system based on mesoporous silica nanoparticles (MSNs-FK506-MECA79). These particles were designed to selectively target high endothelial venules in LNs; this was achieved through surface modification with MECA79 antibodies. Their mean size and zeta potential were 201.18 ± 5.98 nm and - 16.12 ± 0.36 mV, respectively. Our findings showed that MSNs-FK506-MECA79 could accumulate in LNs and increase the local concentration of FK506 from 28.02 ± 7.71 ng/g to 123.81 ± 76.76 ng/g compared with the free FK506 treatment group. Subsequently, the therapeutic efficacy of MSNs-FK506-MECA79 was evaluated in a skin transplantation model. The treatment with MSNs-FK506-MECA79 could lead to a decrease in the infiltration of T cells in the grafts, a reduction in the grade of rejection, and a significant prolongation of survival. Consequently, this study presents a promising strategy for the active LN-targeted delivery of FK506 and improving the immunotherapeutic effects on transplant rejection.

In vivo treatment of zinc phosphide poisoning by administration of mesoporous silica nanoparticles as an effective antidote agent.

Mesoporous silica nanoparticles (MSNs) are highly advanced engineered particles with increased surface area and extreme adsorption capacity for various molecules. Herein, two types of MSNs were synthesized and applied as adsorbents for phosphine gas. One was without functional groups (MSN), and the other was post-modified with boric acid (MSN-BA). The structures of MSN and boric acid-modified MSN with high surface areas of about 1025 and 650 m2/g, respectively, were defined. MSN was found to have particles with sizes around 30 nm by transmission electron microscopy (TEM). In the present study, MSNs were used as an antidote to phosphorus poisoning, and zinc phosphide (phosphorus) powder was used as the toxic and lethal agent. In vivo analysis was carried out on rats to demonstrate the ability of MSNs to chemisorb phosphine gas. In the survival percentage assessment, Phos-poisoned animals were kept alive after treatment with MSNs, and the MSN-BA-treated group (dose of 5 mg/kg) was shown to have a 60 % survival rate. Blood serum analysis showed that MSNs have a high potential to alleviate organ blood damage, and serum biomarkers dropped sharply while phosphine-poisoned animals were treated with MSN-BA.

PEGylated mesoporous silica core-shell redox-responsive nanoparticles for delivering paclitaxel to breast cancer cells.

Controlling the drug release and restricting its presence in healthy organs is extremely valuable. In this study, mesoporous silica nanoparticles (MSN) as the core, loaded with paclitaxel (PTX), were coated with a non-porous silica shell functionalized with disulfide bonds. The nanoparticles were further coated with polyethylene glycol (PEG) via disulfide linkages. We analyzed the physicochemical properties of nanoparticles, including hydrodynamic size via Dynamic Light Scattering (DLS), zeta potential, X-ray Diffraction (XRD) patterns, Fourier-Transform Infrared (FTIR) spectra, and imaging through Transmission Electron Microscopy (TEM) and Scanning Electron Microscopy (SEM). The drug release profile in two distinct glutathione (GSH) concentrations of 2 µM and 10 µM was measured. The cellular uptake of nanoparticles by MCF-7 cell line was determined using Confocal Laser Scanning Microscopy (CLSM) images and flow cytometry. Furthermore, the cell viability and the capability of nanoparticles to induce apoptosis in MCF-7 cell line were studied using the MTT assay and flow cytometry, respectively. Our investigations revealed that the release of PTX from the drug delivery system was redox-responsive. Also, results indicated an elevated level of cellular uptake and efficient induction of apoptosis, underscoring the promising potential of this redox-responsive drug delivery system for breast cancer therapy.

Bioactive mesoporous silica nanoparticle-functionalized titanium implants with controllable antimicrobial peptide release potentiate the regulation of inflammation and osseointegration.

Bacterial infection and delayed osseointegration are two major challenges for titanium-based orthopedic implants. In the present study, we developed a functionalized titanium implant Ti-M@A by immobilizing antimicrobial peptide (AMP) HHC36-loaded diselenide-bridged mesoporous silica nanoparticles (MSNs) on the surface, which showed good long-term and mechanical stability. The functionalized implants can realize the sustained release of AMP over 30 days and exhibit over 95.71 % antimicrobial activity against four types of clinical bacteria (S. aureus, E. coli, P. aeruginosa and MRSA), which arose from the capability to destroy the bacterial membranes. Moreover, Ti-M@A can efficiently inhibit the biofilm formation of the bacteria. The functionalized implants can also significantly promote the osteogenic differentiation of mouse bone marrow-derived mesenchymal stem cells (mBMSCs) because of the Se in MSNs. Notably, it can trigger macrophages toward M2 polarization in vitro by scavenging ROS in LPS-activated macrophages. Consequently, in vivo assays with infection and non-infection bone defect models demonstrated that such bioactive implants can not only kill over 98.82 % of S. aureus, but also promote osseointegration. Hence, this study provides a combined strategy to resolve bacterial infection and delayed osseointegration for titanium implants.

Targeted delivery of elesclomol using a magnetic mesoporous platform improves prostate cancer treatment both in vitro and in vivo.

BACKGROUND: To improve the anticancer properties of elesclomol (ELC), targeted theranostic nanoparticles (NPs; APT-PEG-Au-MMNPs@ELC) were designed to increase the selectivity of the drug delivery system (DDS). MATERIALS AND METHODS: ELC was synthesized and entrapped in the open porous structure of magnetic mesoporous silica nanoparticles (MMNPs). The pore entrance of MMNPs was then blocked using gold gatekeepers. Finally, the external surfaces of the particles were grafted with functional polyethylene glycol (PEG) and EpCAM aptamer to generate biocompatible and targeted NPs. In the next step, the physicochemical properties of prepared NPs were fully evaluated and their anticancer potential was evaluated both in vitro and in vivo. RESULTS: The targeted NPs were successfully synthesized with a final size diameter of 81.13 ± 7.41 nm. The results indicated a pH-dependent release pattern, which sustained for 72 h despite an initial rapid release. Upon exposure to APT-PEG-Au-MMNPs@ELC, higher cytotoxicity was observed in human prostate cancer cells (PC-3) as compared with control Chinese hamster ovary (CHO) cells, indicating higher specificity of targeted NPs against EpCAM-positive cancerous cells. Moreover, APT-PEG-Au-MMNPs@ELC could induce apoptosis in PC-3 cells. In vivo results on a PC-3 xenograft tumor model demonstrated that targeted NPs could significantly inhibit tumor growth and diminish severe side effects of ELC, compared to the free drug. CONCLUSION: Collectively, APT-PEG-Au-MMNPs@ELC could be considered a promising theranostic platform for the targeted delivery of ELC to improve its therapeutic effects in prostate cancer.

Orally Administrated Inflamed Colon-Targeted Nanotherapeutics for Inflammatory Bowel Disease Treatment by Oxidative Stress Level Modulation in Colitis.

Inflammatory bowel disease (IBD) is characterized by an inappropriate and persistent inflammatory immune response and is often accompanied by excessive reactive oxygen species (ROS) production. For effective IBD treatment, there is a high demand for safe and targeted therapy that can be orally administered. In this study, we aimed to propose the use of inflamed colon-targeted antioxidant nanotherapeutics (ICANs) for in situ oxidative stress level modulation in colitis. ICANs consist of mesoporous silica nanoparticles (MSNs) with surface-attached ROS-scavenging ceria nanoparticles (CeNPs), which are further coated with poly(acrylic acid) (PAA) to facilitate preferential adherence to inflamed colon tissues through electrostatic interaction. We achieved a high ROS-scavenging property that remained effective even after artificial gastrointestinal fluid incubation by optimization of the molecular weight and PAA-coating pH. The orally administered ICANs demonstrated enhanced adherence to inflamed colon tissues in an acute inflammation mouse model of IBD induced by dextran sulfate sodium. This targeted delivery resulted in gut microenvironment modulation by regulating redox balance and reducing inflammatory cell infiltration, thereby suppressing the colitis-associated immune response. These findings highlight the potential of noninvasive ICANs as a promising candidate for treating inflammatory intestinal diseases by oxidative stress level modulation in colitis.

A Novel pH-Responsive Iron Oxide Core-Shell Magnetic Mesoporous Silica Nanoparticle (M-MSN) System Encapsulating Doxorubicin (DOX) and Glucose Oxidase (Gox) for Pancreatic Cancer Treatment.

Introduction: This study developed a pancreatic cancer targeted drug delivery system that responds to changes in acidity. The system was based on iron oxide core-shell magnetic mesoporous silica nanoparticles (M-MSNs) to treat pancreatic cancer through combined chemotherapy and starvation therapy. Methods: Glucose oxidase (Gox) was coupled to the cancer cell surface to reduce glucose availability for cancer cells, exacerbating the heterogeneity of the tumor microenvironment. Reduced pH accelerated the depolymerization of pH-sensitive polydopamine (PDA), thereby controlling the spatial distribution of Gox and release of doxorubicin (DOX) within tumor cells. Results: Characterization results showed the successful synthesis of DG@M-MSN-PDA-PEG-FA (DG@NPs) with a diameter of 66.02 ± 3.6 nm. In vitro data indicated DG@NPs were highly effective and stable with good cellular uptake shown by confocal laser scanning microscopy (CLSM). DG@NPs exhibited high cytotoxicity and induced apoptosis. Additionally, in vivo experiments confirmed DG@NPs effectively inhibited tumor growth in nude mice with good biosafety. The combination of starvation therapy and chemotherapy facilitated drug release, suggesting DG@NPs as a novel drug delivery system for pancreatic cancer treatment. Conclusion: This study successfully constructed a doxorubicin release system responsive to acidity changes for targeted delivery in pancreatic cancer, providing a new strategy for combination therapy.

Contact Lens with pH Sensitivity for On-Demand Drug Release in Wearing Situation.

Drug-releasing contact lenses are emerging therapeutic systems for treating ocular diseases. However, their applicability is limited by the burst release of drugs during lens wear and premature drug leakage during packaging, rendering the precise control of release duration or dose difficult. Here, we introduce a pH-sensitive contact lens exhibiting on-demand drug release only during lens wear and negligible premature drug leakage during packaging and transportation, which is accomplished by incorporating drug-loaded mesoporous silica nanoparticles (MSNs) coated with a pH-sensitive polymer into the contact lens. The compositionally optimized pH-sensitive polymer has a lower critical solution temperature (LCST) at >45 °C at pH 7.4, whereas its LCST decreases to <35 °C under acidic conditions (pH ∼ 6.5). Consequently, the MSN-incorporated contact lens sustainably releases the loaded drugs only in the acidic state at 35 °C, which corresponds to lens-wear conditions, through the MSN pores that open because of the shrinkage of polymer chains. Conversely, negligible drug leakage is observed from the contact lens under low-temperature or neutral-pH conditions corresponding to packaging and transportation. Furthermore, compared with the plain contact lens, the pH-sensitive contact lens exhibits good biocompatibility and unchanged bulk characteristics, such as optical (transmittance in the visible-light region), mechanical (elastic modulus and tensile strength), and physical (surface roughness, oxygen permeability, and water content) properties. These findings suggest that the pH-sensitive contact lens can be potentially applied in ocular disease treatment.

Mesoporous silica nanoparticles: An emerging approach in overcoming the challenges with oral delivery of proteins and peptides.

Proteins and peptides (PPs), as therapeutics are widely explored in the past few decades, by virtue of their inherent advantages like high specificity and biocompatibility with minimal side effects. However, owing to their macromolecular size, poor membrane permeability, and high enzymatic susceptibility, the effective delivery of PPs is often challenging. Moreover, their subjection to varying environmental conditions, when administered orally, results in PPs denaturation and structural conformation, thereby lowering their bioavailability. Hence, for effective delivery with enhanced bioavailability, protection of PPs using nanoparticle-based delivery system has gained a growing interest. Mesoporous silica nanoparticles (MSNs), with their tailored morphology and pore size, high surface area, easy surface modification, versatile loading capacity, excellent thermal stability, and good biocompatibility, are eligible candidates for the effective delivery of macromolecules to the target site. This review highlights the different barriers hindering the oral absorption of PPs and the various strategies available to overcome them. In addition, the potential benefits of MSNs, along with their diversifying role in controlling the loading of PPs and their release under the influence of specific stimuli, are also discussed in length. Further, the tuning of MSNs for enhanced gene transfection efficacy is also highlighted. Since extensive research is ongoing in this area, this review is concluded with an emphasis on the potential risks of MSNs that need to be addressed prior to their clinical translation.

Reactive Oxygen Species-Sensitive Biodegradable Mesoporous Silica Nanoparticles Harboring TheraVac Elicit Tumor-Specific Immunity for Colon Tumor Treatment.

Immunotherapy has revolutionized the field of cancer treatment through invigorating robust antitumor immune response. Here, we report the development of a therapeutic vaccine [consisting of high mobility group nucleosome-binding protein 1 (HMGN1), resiquimod/R848, and anti-PD-L1 (αPD-L1)]-loaded reactive oxygen species (ROS)-responsive mesoporous silica nanoparticle (MSN@TheraVac) for curative therapy of colon cancer. In MSN@TheraVac, αPD-L1 conjugated onto the surface of MSNs via a diselenide bond, which can be rapidly released under the oxidative condition of the tumor microenvironment to avert immunosuppression and effector T cell exhaustion while coloaded HMGN1 and R848 would cooperatively trigger robust tumor-infiltrating dendritic cell (TiDC) maturation and elicitation of antitumor immune responses. Indeed, MSN@TheraVac induced the maturation and activation of dendritic cells (DCs) by promoting the surface expression of CD80, CD86, and CD103 as well as the production of pro-inflammatory cytokines, including TNFα, IL-12, and IL-1ß. Importantly, treatment with intravenous MSN@TheraVac led to a complete cure of 100% of BALB/c mice bearing large colon tumors and induced the generation of tumor-specific protective memory without apparent toxicity. Thus, MSN@TheraVac provides a timely release of TheraVac for the curative treatment of colon tumors and holds potential for translation into a clinical therapy for patients with immunologically "cold" colorectal cancers. This ROS-responsive MSN platform may also be tailored for the selective delivery of other cancer vaccines for effective immunotherapy.

A novel and economical approach for the synthesis of short rod-shaped mesoporous silica nanoparticles from coal fly ash waste by Bacillus circulans MTCC 6811.

Coal fly ash (CFA) is an industrial byproduct produced during the production of electricity in thermal power plants from the burning of pulverized coal. It is considered hazardous due to the presence of toxic heavy metals while it is also considered valuable due to the presence of value-added minerals like silicates, alumina, and iron oxides. Silica nanoparticles' demands and application have increased drastically in the last decade due to their mesoporous nature, high surface area to volume ratio, etc. Here in the present research work, short rod-shaped, mesoporous silica nanoparticles (MSN) have been synthesized from coal fly ash by using Bacillus circulans MTCC 6811 in two steps. Firstly, CFA was kept with the bacterial culture for bioleaching for 25 days in an incubator shaker at 120 rpm. Secondly, the dissolved silica in the medium was precipitated with the 4 M sodium hydroxide to obtain a short rod-shaped MSN. The purification of the synthesized silica particle was done by treating them with 1 M HCl at 120 °C, for 90 min. The synthesized short rod-shaped MSN were characterized by UV-vis spectroscopy (UV-Vis), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), Particle size analyzer (PSA), Field emission scanning electron microscopy (FESEM), and transmission electron microscope. The microscopic techniques revealed the short rod-shaped mesoporous silica nanoparticles (MSN) for the final nano-silica, whose size varies from 40 to 80 nm, with an average size of 36 ± 5 nm. The XRD shows the crystalline nature of the synthesized MSN having a crystallite size of 36 nm. The FTIR showed the three characteristic bands in the range of 400-1100 cm-1, indicating the purity of the sample. The energy dispersive X-ray (EDX) showed 53.04 wt% oxygen and 43.42% Si along with 3.54% carbon in the final MSN. The particle size analyzer revealed that the average particle size is 368.7 nm in radius and the polydispersity index (PDI) is 0.667. Such a novel and economical approach could be helpful in the synthesis of silica in high yield with high purity from coal fly ash and other similar waste.

A Dual Concentration-Tailored Cytokine-Chemo Nanosystem to Alleviate Multidrug Resistance and Redirect Balance of Cancer Proliferation and Apoptosis.

Background: Cancer multidrug resistance (MDR) is an important factor that severely affects the chemotherapeutic efficacy. Among various methods to bypass MDR, usage of cytokines, such as tumor necrosis factor alpha (TNFα) is attractive, which exerts antitumor effects of immunotherapeutic response and apoptotic/proinflammatory pathways. Nevertheless, the challenges remain how to implement targeted delivery of TNFα to reduce toxicity and manifest the involved signaling mechanism that subdues MDR. Methods: We synthesized a multifunctional nanosytem, in which TNFα covalently bound to doxorubicin (Dox)-loaded pH-responsive mesoporous silica nanoparticles (MSN) through bi-functional polyethylene glycol (TNFα-PEG-MSN-Hydrazone-Dox) as a robust design to overcome MDR. Results: The salient features of this nanoplatform are: 1) by judicious tailoring of TNFα concentration conjugated on MSN, we observed it could lead to a contrary effect of either proliferation or suppression of tumor growth; 2) the MSN-TNFα at higher concentration serves multiple functions, besides tumor targeting and inducer of apoptosis through extrinsic pathway, it inhibits the expression level of p-glycoprotein (P-gp), a cell membrane protein that functions as a drug efflux pump; 3) the enormous surface area of MSN provides for TNFα functionalization, and the nanochannels accommodate chemotherapeutics, Dox; 4) targeted intracellular release of Dox through the pH-dependent cleavage of hydrazone bonds induces apoptosis by the specific intrinsic pathway; and 5) TNFα-PEG-MSN-Hydrazone-Dox (MSN-Dox-TNFα) could infiltrate deep into the 3D spheroid tumor model through disintegration of tight junction proteins. When administered intratumorally in a Dox-resistant mouse tumor model, MSN-Dox-TNFα exhibited a synergistic therapeutic effect through the collective performances of TNFα and Dox. Conclusion: We hereby develop and demonstrate a multifunctional MSN-Dox-TNFα system with concentration-tailored TNFα that can abrogate the drug resistance mechanism, and significantly inhibit the tumor growth through both intrinsic and extrinsic apoptosis pathways, thus making it a highly potential nanomedicine translated in the treatment of MDR tumors.

Biofunctionalized Decellularized Tissue-Engineered Heart Valve with Mesoporous Silica Nanoparticles for Controlled Release of VEGF and RunX2-siRNA against Calcification.

The goal of tissue-engineered heart valves (TEHV) is to replace normal heart valves and overcome the shortcomings of heart valve replacement commonly used in clinical practice. However, calcification of TEHV is the major bottleneck to break for both clinical workers and researchers. Endothelialization of TEHV plays a crucial role in delaying valve calcification by reducing platelet adhesion and covering the calcified spots. In the present study, we loaded RunX2-siRNA and VEGF into mesoporous silica nanoparticles and investigated the properties of anti-calcification and endothelialization in vitro. Then, the mesoporous silica nanoparticle was immobilized on the decellularized porcine aortic valve (DPAV) by layer self-assembly and investigated the anti-calcification and endothelialization. Our results demonstrated that the mesoporous silica nanoparticles delivery vehicle demonstrated good biocompatibility, and a stable release of RunX2-siRNA and VEGF. The hybrid decellularized valve exhibited a low hemolysis rate and promoted endothelial cell proliferation and adhesion while silencing RunX2 gene expression in valve interstitial cells, and the hybrid decellularized valve showed good mechanical properties. Finally, the in vivo experiment showed that the mesoporous silica nanoparticles delivery vehicle could enhance the endothelialization of the hybrid valve. In summary, we constructed a delivery system based on mesoporous silica to biofunctionalized TEHV scaffold for endothelialization and anti-calcification.

Aptamer/doxorubicin-conjugated nanoparticles target membranous CEMIP2 in colorectal cancer.

The objectives were to identify the functional domains of a potential oncoprotein, cell migration inducing hyaluronidase 2 (CEMIP2), evaluate its expression levels and roles in colorectal cancer (CRC), and develop an aptamer-based nanoparticle for targeted therapy. Data mining on TCGA identified that CEMIP2 might play oncogenic roles in CRC. In a local cohort, CEMIP2 mRNA levels significantly stepwise increase in CRC patients with higher stages, and high CEMIP2 confers worse disease-free survival. In addition, CEMIP2 mRNA levels significantly correlated to hyaluronan levels in sera from CRC patients. Deletion mapping identified that CEMIP2 containing G8 and PANDER-like domains preserved hyaluronidase activity and oncogenic roles, including cell proliferation, anchorage-independent cell growth, cell migration and invasion, and human umbilical vein endothelial cell (HUVEC) tube formation in CRC-derived cells. A customized monoclonal mouse anti-human CEMIP2 antibody probing the PANDER-like domain (anti-289307) counteracted CEMIP2-mediated carcinogenesis in vitro. Cell-SELEX pinpointed an aptamer, aptCEMIP2(101), specifically interacted with the full-length CEMIP2, potentially involving its 3D structure. Treatments with aptCEMIP2(101) significantly reduced CEMIP2-mediated tumorigenesis in vitro. Mesoporous silica nanoparticles (MSN) carrying atpCEMIP2(101) and Dox were fabricated. Dox@MSN, MSN-aptCEMIP2(101), and Dox@MSN-aptCEMIP2(101) significantly suppressed tumorigenesis in vitro compared to the Mock, while Dox@MSN-aptCEMIP2(101) showed substantially higher effects compared to Dox@MSN and MSN-aptCEMIP2(101) in CRC-derived cells. Our study identified a novel oncogene and developed an effective aptamer-based targeted therapeutic strategy.

Biogenesis of Mesoporous Silica Nanoparticles Enclosed in Extracellular Vesicles by Mouse Renal Adenocarcinoma Cells.

Integrating the versatility of synthetic nanoparticles to natural biomaterials, such as cells or cell membranes, has gained considerable attention as promising alternative cargo delivery platforms in recent years. Extracellular vesicles (EVs), natural nanomaterials composed of a protein-rich lipid bilayer secreted by cells, have also shown advantages and great potential as a nano delivery platform in combination with synthetic particles due to their specific natural properties in overcoming several biology hurdles possessed in the recipient cell. Therefore, the preservation of EV's origin properties is critical for their application as nanocarriers. This chapter will describe the encapsulation procedure of MSN encapsulated in EV membrane derived from mouse renal adenocarcinoma (Renca) cells through biogenesis. The FMSN-enclosed EVs produced through this approach still contain preserved EV's natural membrane properties.

The development of a novel copper-loaded mesoporous silica nanoparticle as a peroxidase mimetic for colorimetric biosensing and its application in H2O2 and GSH assay.

In recent years, the development of nanomaterials-based peroxidase mimics as enzyme sensors has been attracting considerable interest due to their outstanding features, including potent stability, and cost-effectiveness toward natural enzymes. In this work, mesoporous silica nanoparticles functionalized by copper (Cu-MSN) were prepared as a new artificial enzyme for the first time through the sol-gel procedure. A comprehensive investigation of the catalytic activity of Cu-MSN was done through the oxidation of chromogenic peroxidase substrates, 3,3',5,5'-tetramethylbenzidine (TMB), and (2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS), in the presence of H2O2. The results indicate that the peroxidase-like activity of the as-prepared sample is significantly higher than other nanoparticles. Additionally, for the study, a facile and rapid sensing method based on the enzyme-like activity of Cu-MSN to detect H2O2 and glutathione (GSH) was developed to examine the potency of the proposed biosensor. Preliminary analysis revealed that the limit of detection (LOD) of H2O2 and GSH is 0.2 and 0.0126 µM, in the range of 0.9-100 and 0.042-1 µM, respectively. These findings support the claims for the efficiency of the sensor in detection fields. Also, human serum was utilized as the real sample to obtain additional evidence.