Temporomandibular joint osteoarthritis (TMJOA) is a commonly encountered degenerative joint disease in oral and maxillofacial surgery. Recent studies have shown that the excessive unbalanced activation of Wnt/β-catenin signaling is connected with the pathogenesis of TMJOA and due to the inability to inhibit the over-activated Wnt pathway, while Wnt16-deficient mice has a more severe Knee OA. However, the efficacy of direct intra-TMJ injection of Wnt16 for the relief of TMJOA is still not directly confirmed. Moreover, small-molecule drugs such as Wnt16 usually exhibit short-lived efficacy and poor treatment adherence. Therefore, in order to obtain a stable release of Wnt16 both in the short and long term, this study fabricates a double-layer slow-release Wnt16 carrier based on mesoporous silica nanospheres (MSNs) encased within hyaluronic acid (HA) hydrogels. The biofunctional hydrogel HA/Wnt16@MSN is analyzed both in vitro and in vivo to evaluate the treatment of TMJOA. As a result, it shows superior pro-cartilage matrix restoration and inhibition of osteoclastogenesis ability, and effectively inhibits the over-activation of the Wnt/β-catenin pathway. Taken together, biofunctional hydrogel HA/Wnt16@MSN is a promising candidate for the treatment of TMJOA.

Advanced breast cancer remains a significant oncological challenge, requiring new approaches to improve clinical outcomes. This study investigated an innovative theranostic agent using the MCM-41-NH2-DTPA-Gd3⁺-MIH nanomaterial, which combined MRI imaging for detection and a novel chemotherapy agent (MIH 2.4Bl) for treatment. The nanomaterial was based on the mesoporous silica type, MCM-41, and was optimized for drug delivery via functionalization with amine groups and conjugation with DTPA and complexation with Gd3+. MRI sensitivity was enhanced by using gadolinium-based contrast agents, which are crucial in identifying early neoplastic lesions. MIH 2.4Bl, with its unique mesoionic structure, allows effective interactions with biomolecules that facilitate its intracellular antitumoral activity. Physicochemical characterization confirmed the nanomaterial synthesis and effective drug incorporation, with 15% of MIH 2.4Bl being adsorbed. Drug release assays indicated that approximately 50% was released within 8 h. MRI phantom studies demonstrated the superior imaging capability of the nanomaterial, with a relaxivity significantly higher than that of the commercial agent Magnevist. In vitro cellular cytotoxicity assays, the effectiveness of the nanomaterial in killing MDA-MB-231 breast cancer cells was demonstrated at an EC50 concentration of 12.6 mg/mL compared to an EC50 concentration of 68.9 mg/mL in normal human mammary epithelial cells (HMECs). In vivo, MRI evaluation in a 4T1 syngeneic mouse model confirmed its efficacy as a contrast agent. This study highlighted the theranostic capabilities of MCM-41-NH2-DTPA-Gd3⁺-MIH and its potential to enhance breast cancer management.

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.

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.

BACKGROUND: 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.
METHODS: 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-1β, and iNOS), better inhibited the progress of periodontitis and induced tissue regeneration without showing significant toxic side effects in cells.
CONCLUSIONS: This system provides a promising strategy for the design of intelligent, efficient, and safe anti-periodontitis drug delivery systems.

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.

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.

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.

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.

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.