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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., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

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., (Copyright © 2024 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.)

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-NH 2 -DTPA-Gd 3 ⁺-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 Gd 3+ . 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 EC 50 concentration of 12.6 mg/mL compared to an EC 50 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-NH 2 -DTPA-Gd 3 ⁺-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.

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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-1β, 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., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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 m 2 /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., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

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 Fe 3 O 4 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., (© 2024. The Author(s).)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

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., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Yingjun Wang, Jiyu Dong, Lin Wang, Dan Shao has patent #202210242685.5 pending to South China University of Technology., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

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.

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.

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., Competing Interests: Declaration of Competing Interest Declared none., (Copyright © 2023 Elsevier B.V. All rights reserved.)

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., Competing Interests: No potential conflict of interest was reported by the authors., (© 2023 Qi et al.)

Immunotherapy has revolutionized the field of cancer treatment through invigorating robust antitumor immune response. Here, we report the development of a thera peutic vac cine [consisting of high mobility group nucleosome-binding protein 1 (HMGN1), resiquimod/R848, and anti-PD-L1 (αPD-L1)]-loaded reactive oxygen species (ROS)-responsive m esoporous s ilica n anoparticle ( 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-1β. 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.

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., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

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 H 2 O 2 . 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 H 2 O 2 and glutathione (GSH) was developed to examine the potency of the proposed biosensor. Preliminary analysis revealed that the limit of detection (LOD) of H 2 O 2 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., (© 2023. The Author(s), under exclusive licence to The Japan Society for Analytical Chemistry.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

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., Competing Interests: The authors have declared that no competing interest exists in this work., (© 2023 Hsia et al.)

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.

In recent years, injectable stimuli-sensitive hydrogels are employed as suitable drug delivery carriers for the release of various anti-cancer drugs. However, large pore size of the microporous hydrogel trigger release of small molecular anticancer drug that limits hydrogel application in cancer therapy. Therefore, introducing reinforcing fillers such as mesoporous silica nanoparticles (MSNs) can not only load different type of anticancer drugs but also prevent the premature release of drugs due to the strengthening of the networks. Furthermore, high specific surface area, suitable size, large pore volume, and stable physicochemical properties of MSNs can improve the therapeutic efficacy. In this study, to sustain the release of hydrophobic anticancer drug, camptothecin (CPT) was loaded into MSNs, and then imbibed into the physiological stimuli-sensitive poly(ethylene glycol)-poly(β-aminoester urethane) (PAEU) hydrogels. MSN-imbibed PAEU hydrogels exhibited prolonged release of CPT than MSNs and PAEU hydrogel alone. Furthermore, MSN-imbibed PAEU copolymers form stable viscoelastic gel depot into the subcutaneous layers of Sprague-Dawley rats and found to be safe and not induced toxicity to healthy organs, implying biodegradability and safety of the hydrogels. Interestingly, CPT-loaded hydrogels shown dose-dependent toxicity to A549 and B16F10 cells. These results demonstrated that MSN-imbibed PAEU hydrogel with biocompatible, biodegradable, and in situ gel forming property could be a useful drug delivery depot for sustained release of anticancer drugs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Interfacial nanobubbles on a superhydrophobic surface can serve as ultrasound cavitation nuclei for continuously promoting sonodynamic therapy, but their poor dispersibility in blood has limited their biomedical application. In this study, we proposed ultrasound-responsive biomimetic superhydrophobic mesoporous silica nanoparticles, modified with red blood cell membrane and loaded with doxorubicin (DOX) (F-MSN-DOX@RBC), for RM-1 tumor sonodynamic therapy. Their mean size and zeta potentials were 232 ± 78.8 nm and -35.57 ± 0.74 mV, respectively. The F-MSN-DOX@RBC accumulation in a tumor was significantly higher than in the control group, and the spleen uptake of F-MSN-DOX@RBC was significantly reduced in comparison to that of the F-MSN-DOX group. Moreover, the cavitation caused by a single dose of F-MSN-DOX@RBC combined with multiple ultrasounds provided continuous sonodynamic therapy. The tumor inhibition rates in the experimental group were 71.5 8 ± 9.54%, which is significantly better than the control group. DHE and CD31 fluorescence staining was used to assess the reactive oxygen species (ROS) generated and the broken tumor vascular system induced by ultrasound. Finally, we can conclude that the combination of anti-vascular therapy, sonodynamic therapy by ROS, and chemotherapy promoted tumor treatment efficacy. The use of red blood cell membrane-modified superhydrophobic silica nanoparticles is a promising strategy in designing ultrasound-responsive nanoparticles to promote drug-release.

The blood-brain barrier (BBB) acts as a physical/biochemical barrier that protects brain parenchyma from potential hazards exerted by different xenobiotics found in the systemic circulation. This barrier is created by "a lipophilic gate" as well as a series of highly organized influx/efflux mechanisms. The BBB bottleneck adversely affects the efficacy of chemotherapeutic agents in treating different CNS malignancies such as glioblastoma, an aggressive type of cancer affecting the brain. In the present study, mesoporous silica nanoparticles (MSNs) were conjugated with the transactivator of transcription (TAT) peptide, a cell-penetrating peptide, to produce MSN-NH-TAT with the aim of improving methotrexate (MTX) penetration into the brain. The TAT-modified nanosystem was characterized by Fourier transform infrared spectrometry (FTIR), field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), atomic force microscopy (AFM), dynamic light scattering (DLS), and N 2 adsorption-desorption analysis. In vitro hemolysis and cell viability studies confirmed the biocompatibility of the MSN-based nanocarriers. In addition, in vivo studies showed that the MTX-loaded MSN-NH-TAT improved brain-to-plasma concentration ratio, brain uptake clearance, and the drug's blood terminal half-life, compared with the use of free MTX. Taken together, the results of the present study indicate that MSN functionalization with TAT is crucial for delivery of MTX into the brain. The present nanosystem represents a promising alternative drug carrier to deliver MTX into the brain via overcoming the BBB.

The characteristics of global prevalence and high recurrence of bladder cancer has led numerous efforts to develop new treatments. The spontaneous voiding and degradation of the chemodrug hamper the efficacy and effectiveness of intravesical chemotherapy following tumor resection. Herein, the externally thiolated hollow mesoporous silica nanoparticles (MSN-SH(E)) is fabricated to serve as a platform for improved bladder intravesical therapy. Enhanced mucoadhesive effect of the thiolated nanovector is confirmed with porcine bladder. The permeation-enhancing effect is also verified, and a fragmented distribution pattern of a tight junction protein, claudin-4, indicates the opening of tight junction. Moreover, MSN-SH(E)-associated reprogramming of M2 macrophages to M1-like phenotype is observed in vitro. The antitumor activity of the mitomycin C (MMC)-loaded nanovector (MMC@MSN-SH(E)) is more effective than that of MMC alone in both in vitro and in vivo. In addition, IHC staining is used to analyze IFN-γ, TGF-β1, and TNF-α. These observations substantiated the significance of MMC@MSN-SH(E) in promoting anticancer activity, holding the great potential for being used in intravesical therapy for non-muscle invasive bladder cancer (NMIBC) due to its mucoadhesivity, enhanced permeation, immunomodulation, and prolonged and very efficient drug exposure., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Poly (methyl methacrylate) (PMMA) is a commonly used material for the fabrication of biomedical appliances. Although PMMA has several advantages, it is susceptible to microbial insults with practical use. Therefore, different bioactive nanomaterials, such as nanoceria (CeN), have been proposed to enhance the properties of PMMA. In this study, we investigated the effect of the incorporation of CeN into PMMA with and without the use of mesoporous silica nanoparticle (SBA-15) carriers. The unmodified PMMA specimens (control, CTRL) were compared to groups containing SBA-15, CeN, and the synthesized SBA-15 impregnated with CeN (SBA-15@CeN) at different loading percentages. The mechanical and physical properties of the different SBA-15@CeN groups and their effects on cell viability were investigated, and the optimal CeN concentration was identified accordingly. Our results revealed that flexural strength was significantly (P < 0.01) reduced in the SBA-15@CeN 3× group (containing 3-fold the CeN wt. %). Although the surface microhardness increased with the increase in the wt. % of SBA-15@CeN, cell viability was significantly reduced (P < 0.001). The SBA-15@CeN 1× group had the optimal concentration and displayed significant resistance to single-and multispecies microbial colonization. Finally, the enzymatic activity of CeN was significantly high in the SBA-15@CeN 1× group. The proinflammatory markers (IL-6, IL-1β, TNF-α, CD80, and CD86) showed a significant (P < 0.001) multifold reduction in lipopolysaccharide-induced RAW cells treated with a 5-day eluate of the SBA-15@CeN 1× group. These results indicate that the addition of SBA-15@CeN at 1.5 wt % improves the biological response of PMMA without compromising its mechanical properties., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Liver cancer, especially hepatocellular carcinoma, is an important cause of cancer-related death, and its incidence is increasing worldwide. Nano drug delivery systems have shown great promise in the treatment of cancers. In order to improve their therapeutic efficacy, it is very important to realize the high accumulation and effective release of drugs at the tumor site. In this manuscript, using doxorubicin (DOX) as a model drug, CD13-targeted mesoporous silica nanoparticles coated with NGR-peptide-modified pegylated carboxymethyl chitosan were constructed (DOX/MSN-CPN). DOX/MSN-CPN comprises a spherical shape with an obvious capping structure and a particle size of 125.01 ± 1.52 nm. With a decrease in pH, DOX/MSN-CPN showed responsive desorption from DOX/MSN-CPN and pH-responsive release of DOX was observed. Meanwhile, DOX/MSN-CPN could be efficiently absorbed through NGR-mediated internalization in vitro and could efficiently deliver DOX to tumor tissues with long accumulation times in vivo, suggesting good active targeting properties. Moreover, significant tumor inhibition has been observed in antitumor studies in vivo. This study provides a strategy of utilizing DOX/MSN-CPN as a nano-platform for drug delivery, which has superb therapeutic efficacy and safety for the treatment of hepatocellular carcinoma both in vivo and in vitro.

Cancer is a disease of global importance. In order to mitigate conventional chemotherapy-related side effects, phytochemicals with inherent anticancer efficacy have been opted. However, the use of nanotechnology is essential to enhance the bioavailability and therapeutic efficacy of these phytochemicals. Herein, we have formulated folic acid conjugated polyacrylic acid capped mesoporous silica nanoparticles (∼47.6 nm in diameter) for pH-dependent targeted delivery of chrysin to breast cancer (MCF-7) cells. Chrysin loaded mesoporous silica nanoparticles (Chr- mSiO 2 @PAA/FA) have been noted to induce apoptosis in MCF-7 cells through oxidative insult and mitochondrial dysfunction with subsequent G 1 arrest. Further, in tumor bearing mice, intravenous incorporation of Chr-mSiO 2 @PAA/FA has been noticed to enhance the anti-neoplastic effects of chrysin via tumor site-specific accumulation. Enhanced cytotoxicity of chrysin contributed towards in vivo tumor regression, restoration of normalized tissue architecture and maintenance of healthy body weight. Besides, no serious systemic toxicity was manifested in response to Chr-mSiO 2 @PAA/FA administration in vivo. Thus, the study evokes about the anticancer potentiality of chrysin and its increased therapeutic activity via incorporation into folic acid conjugated mesoporous silica nanoparticles, which may hold greater impact in field of future biomedical research., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Ocular vascular diseases are the major causes of visual impairment, which are characterized by retinal vascular dysfunction and robust inflammatory responses. Traditional anti-angiogenic or anti-inflammatory drugs still have limitations due to the short-acting effects. To improve the anti-angiogenic or anti-inflammatory efficiency, a dual-drug nanocomposite formulation was proposed for combined anti-angiogenic and anti-inflammatory treatment of ocular vascular diseases., Methods : CBC-MCC@hMSN(SM) complex nanoformulation was prepared by integrating conbercept (CBC, an anti-angiogenic drug) and MCC950 (MCC, an inhibitor of inflammation) into the surface-modified hollow mesoporous silica nanoparticles (hMSN(SM)). CBC-MCC@hMSN(SM) complex nanoformulation was then characterized by Fourier transform infrared spectroscopy, transmission electron microscopy, zeta potentials, and nitrogen adsorption-desorption measurement. CBC and MCC release profile, cytotoxicity, tissue toxicity, anti-angiogenic effects, and anti-inflammatory effects of CBC-MCC@hMSN(SM) were estimated using the in vitro and in vivo experiments., Results:  CBC-MCC@hMSN(SM) complex had no obvious cytotoxicity and tissue toxicity and did not cause a detectable ocular inflammatory responses. CBC-MCC@hMSN(SM) complex was more effective than free CBC or MCC in suppressing endothelial angiogenic effects and inflammatory responses in vitro. A single intraocular injection of CBC-MCC@hMSN(SM) complex potently suppressed diabetes-induced retinal vascular dysfunction, choroidal neovascularization, and inflammatory responses for up to 6 months., Conclusion : Combined CBC and MCC nanoformulation provides a promising strategy for sustained suppression of pathological angiogenesis and inflammatory responses to improve the treatment outcomes of ocular vascular diseases., Competing Interests: The authors have no conflicts of interest to declare for this work., (© 2023 Sun et al.)

The poor penetration of nanocarriers within tumor dense extracellular matrices (ECM) greatly restricts the access of anticancer drugs to the deep tumor cells, resulting in low therapeutic efficacy. Moreover, the high toxicity of the traditional chemotherapeutics inevitably causes undesirable side effects. Herein, taking the advantages of biosafe H 2 and small-sized nanoparticles in diffusion within tumor ECM, we develop a matrix metalloprotease 2 (MMP-2) responsive size-switchable nanoparticle (UAMSN@Gel-PEG) that is composed of ultrasmall amino-modified mesoporous silica nanoparticles (UAMSN) wrapped within a PEG-conjugated gelatin to deliver H 2 to the deep part of tumors for effective gas therapy. Ammonia borane (AB) is chosen as the H 2 prodrug that can be effectively loaded into UAMSN by hydrogen-bonding adsorption. Gelatin is used as the substrate of MMP-2 to trigger size change and block AB inside UAMSN during blood circulation. PEG is introduced to further increase the particle size and endow the nanoparticle with long blood circulation to achieve effective tumor accumulation via the EPR effect. After accumulation into the tumor site, MMP-2 promptly digests gelatin to expose UAMSN loading AB for deep tumor penetration. Upon stimulation by the acidic tumor microenvironment, AB decomposes into H 2 for further intratumor diffusion to achieve effective hydrogen therapy. Consequently, such a simultaneous deep tumor penetration of nanocarriers and H 2 results in an evident suppression on tumor growth in a 4T1 tumor-bearing model without any obvious toxicity on normal tissues. Our synthetic nanosystem provides a promising strategy for the development of nanomedicines with enhanced tumor permeability and good biosafety for efficient tumor treatment.

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., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Unicellular bacterial cells exhibit diverse population behaviors (i.e., aggregation, dispersion, directed assembly, biofilm formation, etc.) to facilitate communication and cooperation. Suitable bacterial behaviors are required for efficient nutrient uptake, cell recycling, and stress response for environmental and industrial application of bacterial populations. However, it remains a great challenge to artificially control bacterial behaviors because of complicated genetic and biochemical mechanisms. In this study, we designed facile mesoporous silica nanoparticle (MSN)-based assemblies to intelligently regulate bacterial behaviors with the help of light and magnetic field. This system was composed of magnetic MSNs, i.e., MnFe 2 O 4 @CoFe 2 O 4 @MSN modified by photoactive spiropyran (SP), and the chitosan-based polymers ChiPSP, i.e., chitosan grafted by triphenylphosphine and SP. The assembly strongly bound bacterial cells, inducing reversible bacterial aggregation by visible-light irradiation and dark. Moreover, the formed bacterial aggregates could be further governed by a directed magnetic field (DMF) to form microfibers and by an alternating magnetic field (AMF) to form biofilms. This study realized stimulus-triggered regulation of bacterial behaviors by MSNs and implied the great power of chemical strategies in intelligent control of diverse biological processes for environmental and industrial applications.

Micro-ribonucleic acid (miRNA)-based therapies show advantages for bone regeneration but need efficient intracellular delivery methods. Inorganic nanoparticles such as mesoporous bioactive glass nanoparticles (MBGN) and mesoporous silica nanoparticles (MSN) have received growing interest in the intracellular delivery of nucleic acids. This study explores the capacity of MBGN and MSN for delivering miRNA to bone marrow mesenchymal stem cells (BMSC) for bone regenerative purposes, with a focus on comparing the two in terms of cell viability, transfection efficiency, and osteogenic actions. Spherical MBGN and MSN with a particle size of ~200 nm and small-sized mesopores were prepared using the sol-gel method, and then the surface was modified with polyethyleneimine for miRNA loading and delivery. The results showed miRNA can be loaded into both nanoparticles within 2 h and was released sustainedly for up to 3 days. Confocal laser scanning microscopy and flow cytometry analysis indicated a high transfection efficiency (>64%) of both nanoparticles without statistical difference. Compared with MSN, MBGN showed stronger activation of alkaline phosphatase and activation of osteocalcin genes. This translated to a greater osteogenic effect of MBGN on BMSC, with Alizarin red staining showing greater mineralization compared with the MSN group. These findings show the potential for MBGN to be used in bone tissue engineering.

The differential tumor environment guides various antitumor drug delivery strategies for efficient cancer treatment. Here, based on the special bacteria-enriched tumor environment, we report a different drug delivery strategy by targeting bacteria inhabiting tumor sites. With a tissue microarray analysis, it was found that bacteria amounts displayed significant differences between tumor and normal tissues. Bacteria-targeted mesoporous silica nanoparticles decorated with bacterial lipoteichoic acid (LTA) antibody (LTA-MSNs) could precisely target bacteria in tumors and deliver antitumor drugs. By the intravenous administration of bacteria-targeted nanoparticles, we showed in mice with colon cancer, lung cancer, and breast cancer that LTA-MSNs exhibited a high tumor-targeting ability. As a proof-of-concept study, tumor microbes as some of the characteristics of a tumor environment could be utilized as potential targets for tumor targeting. This bacteria-guided tumor-targeting strategy might have great potential in differential drug delivery and cancer treatment.

This review focuses on the biomedical application of mesoporous silica nanoparticles (MSNs), mainly focusing on the therapeutic application of MSNs for cancer treatment and specifically on overcoming the challenges of currently available anthelmintics (e.g., low water solubility) as repurposed drugs for cancer treatment. MSNs, due to their promising features, such as tunable pore size and volume, ability to control the drug release, and ability to convert the crystalline state of drugs to an amorphous state, are appropriate carriers for drug delivery with the improved solubility of hydrophobic drugs. The biomedical applications of MSNs can be further improved by the development of MSN-based multimodal anticancer therapeutics (e.g., photosensitizer-, photothermal-, and chemotherapeutics-modified MSNs) and chemical modifications, such as poly ethyleneglycol (PEG)ylation. In this review, various applications of MSNs (photodynamic and sonodynamic therapies, chemotherapy, radiation therapy, gene therapy, immunotherapy) and, in particular, as the carrier of anthelmintics for cancer therapy have been discussed. Additionally, the issues related to the safety of these nanoparticles have been deeply discussed. According to the findings of this literature review, the applications of MSN nanosystems for cancer therapy are a promising approach to improving the efficacy of the diagnostic and chemotherapeutic agents. Moreover, the MSN systems seem to be an efficient strategy to further help to decrease treatment costs by reducing the drug dose.

New strategies to decrease risk of relapse after surgery are needed for improving 5-year survival rate of hepatocellular carcinoma (HCC). To address this need, a wound-targeted nanodrug is developed, that contains an immune checkpoint inhibitor (anti-PD-L1)and an angiogenesis inhibitor (sorafenib)). These nanoparticles consist of highly biocompatible mesoporous silica (MSNP) that is surface-coated with platelet membrane (PM) to achieve surgical site targeting in a self-amplified accumulation manner. Sorafenib is introduced into the MSNP pores while covalently attaching anti-PD-L1 antibody on the PM surface. The resulting nano-formulation, abbreviated as a-PM-S-MSNP, can effectively target the surgical margin when intraperitoneally (IP) administered into an immune competent murine orthotopic HCC model. Multiple administrations of a-PM-S-MSNP generate potent anti-HCC effect and significantly prolong overall mice survival. Immunophenotyping and immunochemistry staining reveal the signatures of favorable anti-HCC immunity and anti-angiogenesis effect at tumor sites. More importantly, microscopic inspection of a-PM-S-MSNP treated mice shows that 2 out 6 are histologically tumor-free, which is in sharp contrast to the control mice where tumor foci can be easily identified. The data suggest that a-PM-S-MSNP can efficiently inhibit post-surgical HCC relapse without obvious side effects and holds considerable promise for clinical translation as a novel nanodrug., (© 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.)

A significant bottleneck in the clinical translation of stem cells remains eliciting the desired stem cell behavior once transplanted in the body. In their natural environment, stem cell fate is regulated by their interaction with extracellular matrix (ECM), mainly through integrin-mediated cell adhesion. 2D biointerfaces that selectively present ECM-derived ligands can be used as valuable tools to study and improve our understanding on how stem cells interact with their environment. Here we developed a new type of biointerface based on mesoporous silica nanoparticles (MSN) which are interesting nanomaterials for biointerface engineering because they allow close control over surface physiochemical properties. To create the platform, DNA functionalized MSN (MSN-ssDNA) with varying PEG linker length were developed. Cell adhesion tripeptide RGD was conjugated to a complementary DNA strand, which could specifically bind to MSN-ssDNA to create MSN-dsDNA-RGD films. We showed that MSN-dsDNA-RGD films could promote hMSCs adhesion and spreading, whereas MSN-dsDNA films without RGD resulted in poor cell spreading with round morphology, and low cell adhesion. In addition, we showed that cell adhesion to the films is PEG length-dependent. The design of the platform allows easy incorporation of other and multiple ECM ligands, as well as soluble cues, making MSN-ssDNA based biointerfaces a novel tool to study ligand-stem cell interactions., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Aims: Synthesis of novel drug delivery system for targeted delivery of cuminaldehyde to breast cancer cells and the subsequent analyses of anti-neoplastic potential of the drug., Main Methods: 3-carboxy-phenyl boronic acid (PBA) conjugated and polyacrylic acid (PAA) gated mesoporous silica nanoparticles (MSNs) were synthesized for the targeted delivery of cuminaldehyde (CUM) to breast cancer cells. Enhancement of anti-neoplastic effects of cuminaldehyde (4-isopropylbenzaldehyde) by the nanoconjugates was assessed., Key Findings: The anti-cancer effects of non-targeted and targeted drug-nanoconjugates were examined in vitro and in vivo. The targeted drug-nanoconjugates caused cell cycle arrest and induced the intrinsic pathway of apoptosis in MCF-7 cells through mitochondrial damage. In vivo intravenous injection of the targeted drug-nanoconjugates led to effective reduction in growth of 4 T1 induced mammary pad tumor in female BALB/c mice via augmented accumulation of cuminaldehyde. The drug-nanoconjugates did not exhibit any systemic toxicity., Significance: Therefore, MSN-PBA-CUM-PAA represents a potent therapeutic model for breast cancer treatment., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Mesoporous silica nanoparticles (MSNs) are widely used in many biomedical applications and clinical fields. However, the applications of MSNs are limited by their severe toxicity. Apigenin (AG) has demonstrated pharmacological effects with low toxicity. The aim of this study was to clarify the role of AG in the progression of MSNs-induced renal injury. BALB/c mice and NRK-52E cells were exposed to MSNs with or without AG. AG protected mice and NRK-52E cells from the MSNs-induced pathological variations in renal tissues and decreased cell viability. AG significantly reduced the levels of serum blood urea nitrogen (BUN) and serum creatinine (Scr), upregulated the levels of superoxide dismutase (SOD), glutathione (GSH) and catalase (CAT), and improved the pathological changes of the kidney in MSNs-treated mice. The protective effects of AG were associated with its ability to increase the levels of antioxidants, reduce the accumulation of ROS, and inhibit the expression of the inflammatory mediators (TNF-α, IL-6). In addition, AG treatment upregulated the activity of FOXO3a, increased the level of IkBα, and reduced the nuclear translocation of NF-κB, which ultimately alleviated MSNs-induced inflammation. Nuclear FOXO3a translocation also triggered antioxidant gene transcription and protected nephrocyte from oxidative damage. However, knockdown of FOXO3a significantly blocked the protective effects of AG. These findings suggested that AG could be a promising therapeutic strategy for MSNs-induced nephrotoxicity, and this protective effect might be related to the suppression of oxidative stress and inflammation via the FOXO3a/NF-κB pathway., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Despite its prominent therapeutic efficacy, chemotherapy has raised serious concerns due to the severe adverse effects and multidrug resistance evoked, which propels the search for safe and green therapeutic agents. BAMLET (bovine α-lactalbumin made lethal against tumor cell) is a well-known protein-based anticancer agent of selective tumoricidal activity. Here, we prepared oleic acid-modified mesoporous silica nanoparticles (OA-MSNs) conjugated with bovine α-lactalbumin, a lipoprotein complex resembling BAMLET formed on the surface of MSNs (MSN-BAMLET) to load the anticancer drug of docetaxel (DTX). Compared to that of OA-MSNs/DTX, the obtained MSN-BAMLET/DTX with a sustained and pH-responsive drug release behaviors exhibited good biocompatibility and enhanced cytotoxic effect against cancer cells. Moreover, the presence of lipoprotein complex in MSN-BAMLET contributed to the improved dispersion of the composite in solution and the inhibitory effect on the migration of cancer cells. Furthermore, the adsorption profiles of protein corona on the obtained nanoparticles were analyzed. It was found that the marked low amount and abundance of plasma proteins were adsorbed on the α-lactalbumin coated siliceous composite demonstrated its long circulation property. Finally, in vivo study showed that MSN-BAMLET/DTX contributed to the effective cancer ablation and the prolonged survival. Therefore, the constructed MSN-BAMLET of the mesoregular structure and peculiar tumoricidal effect provides a manipulable nanoplatform as drug nanocarrier for therapeutic applications., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Traditional treatment of cancers such as chemotherapy still causes many side effects after the treatment even nowadays, therefore combination therapies by using drug delivery systems are valued by more and more scientists. However, loading multiple drugs in the nanoparticles for drug delivery system may cause insufficient drugs or functional groups, which might let the nanomaterial have fewer functions. Therefore, making the mesoporous silica nanoparticles (MSNs) have photodynamic therapy function by "doping " lanthanide ions into the material structure, can evade this problem. Moreover, with the doping of lanthanide metals, the MSNs can have not only dual imaging functions of both magnetic resonance imaging and fluorescence, but also achieve photodynamic function. To feature the material with more function, chemotherapeutic drug-doxorubicin was loaded into the pores of MSNs and then bonded hyaluronic acid which is the active target and a gatekeeper, on the surface of MSNs. Finally, an all-in-one drug delivery system" Hyaluronidase and pH-responsive mesoporous silica nanoparticles with dual-imaging activity for chemo-photodynamic therapy" is synthesized. The first part in this experiment was to confirm the physical properties of the lanthanides dopped MSN and its photodynamic treatment effect. The second part was to confirm that each organic molecule had been successfully bonded to the surface of the MSN and achieve pH and Hyaluronidase response drug release effect, The last part was to prove that the drug delivery system had a significant anticancer effect through cell experiments., (Copyright © 2022 Elsevier Inc. All rights reserved.)

This work was developed to the effects of biofilm composite nano-drug delivery system (OMVs-MSN-5-FU) on lymph node metastasis from oral squamous cell carcinoma. Mesoporous silica nanoparticles loaded with 5-FU (MSN-5-FU) were prepared first. Subsequently, the outer membrane vesicles (OMV) of Escherichia coli were collected to wrap MSN-5-FU, and then OMVs-MSN-5-FU was prepared. It was then immersed in artificial gastric juice and artificial intestinal juice to explore the drug release rate. Next, the effects of different concentrations of the nano-drug delivery systems on the proliferation activity of oral squamous carcinoma cell line KOSC-2 cl3-43 were analyzed. Tumor-bearing nude mice models were prepared by injecting human tongue squamous cell carcinoma cells Tca8113 into BALB/c-nu nude mice. They were injected with the OMVs-MSN-5-FU nano drug carrier system, and peri-carcinoma tissue and cervical lymph node tissue were harvested to observe morphological changes by Hematoxylin - eosin (HE) staining. The scanning electron microscope (SEM) results showed that all MSN, MSN-5-FU, OMV, and OMV-MSN-5-FU were spherical and uniformly distributed, with particle sizes of about 60nm, 80nm, 90nm, and 140nm, respectively. Among them, OMV had a directional core-shell structure. The cumulative drug release rates of artificial gastric juice in 48 hours were 61.2 ± 2.3% and 26.5 ± 3.1%, respectively. The 48 hours cumulative drug release rates of artificial intestinal juice were 70.5 ± 6.3% and 32.1 ± 3.8%, respectively. The cumulative release of MSN-5-FU was always higher than OMV-MSN-5-FU. The cumulative release of MSN-5-FU was always higher than OMV-MSN-5-FU. After injection of OMVS-MSN-5-FU, the number of cancer cells was significantly reduced and cervical lymph node metastasis was significantly controlled. HE staining results showed that OMVS-MSN-5-FU injection reduced the number of stained cells. Dense lymphocytes were clearly observed in the cortex of neck lymphocytes. The OMVs-MSN-5-FU drug delivery system can slow down the drug release rate, significantly inhibit the proliferation activity of oral squamous cancer cells, and control the metastasis of cancer cells to cervical lymph nodes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Huang, Wu and Xu.)

The clinical utilization of fenbendazole (FBZ) as a potential anticancer drug has been limited due to its low water solubility, which causes its low bioavailability. The development of a drug nanoformulation that includes the solubilizing agent as a drug carrier can improve solubility and bioavailability. In this study, Mobil Composition of Matter Number 48 (MCM-48) nanoparticles were synthesized and functionalized with succinylated β-lactoglobulin (BLG) to prevent early-burst drug release. The BLG-modified amine-functionalized MCM-48 (MCM-BLG) nanoparticles were loaded with FBZ to produce the drug nanoformulation (FBZ-MCM-BLG) and improved the water solubility and, consequently, its anticancer effects against human prostate cancer PC-3 cells. The prepared FBZ-MCM-BLG was characterized in terms of size, zeta potential, drug loading capacity, morphology, thermal and chemical analyses, drug release, cellular uptake, cell viability, cell proliferation, production of reactive oxygen species (ROS), and cell migration. The results demonstrated that the FBZ-MCM-BLG nanoparticles have a spherical morphology with a size and zeta potential of 369 ± 28 nm and 28 ± 0.4 mV, respectively. The drug loading efficiency of the new nanoformulation was 19%. The release of FBZ was pH-dependent; a maximum cumulative release of about 76 and 62% in 12 h and a burst release of 53 and 38% in the first 0.5 h was observed at pH 1.2 and 6.8, respectively. The prepared FBZ-MCM-BLG formulation demonstrated higher cytotoxicity effects against PC-3 cells by 5.6- and 1.8-fold, respectively, when compared to FBZ and FBZ-MCM nanoparticles. The new formulation also increased the production of ROS by 1.6- and 1.2-fold and inhibited the migration of PC-3 cells when compared to the FBZ and FBZ-MCM nanoparticles, respectively. Overall, FBZ-MCM-BLG nanoparticles improved FBZ delivery to PC-3 cells and have the potential to be evaluated for the treatment of prostate cancer following a comprehensive in vivo study.

Magnetic resonance molecular imaging can provide anatomic, functional and molecular information. However, because of the intrinsically low sensitivity of magnetic resonance imaging (MRI), high-performance MRI contrast agents are required to generate powerful image information for image diagnosis. Herein, we describe a novel T 1 contrast agent with magnetic-imaging properties facilitated by the gadolinium oxide (Gd 2 O 3 ) doping of mesoporous silica nanoparticles (MSN). The size, morphology, composition, MRI relaxivity ( r 1 ), surface area and pore size of these nanoparticles were evaluated following their conjugation with Gd 2 O 3 to produce Gd 2 O 3 @MSN. This unique structure led to a significant enhancement in T 1 contrast with longitudinal relaxivity ( r 1 ) as high as 51.85 ± 1.38 mM -1 s -1 . Gd 2 O 3 @MSN has a larger T 1 relaxivity than commercial gadolinium diethylene triamine pentaacetate (Gd-DTPA), likely due to the geometrical confinement effect of silica nanoparticles. These results suggest that we could successfully prepare a novel high-performance T 1 contrast agent, which may be a potential candidate for in-vivo MRI., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Guo, Zhang, Li and Hao.)

Nanoparticle-based targeting of overexpressed cell-surface receptors is a promising strategy that provides precise delivery of drugs to cancer cells. In the present study, we developed highly reproducible and monodispersed, chitosan-coated (pH-responsive), doxorubicin-loaded, aptamer-mesoporous silica nanoparticle (MSN) bioconjugates for actively targeting breast cancer cells harboring overexpression of EGF receptors (EGFR/HER2). The developed targeted MSNs demonstrated higher uptake and cytotoxicity of triple negative and HER2 positive breast cancer cells when compared to non-targeted MSNs. The chitosan coating imparted pH-responsiveness and endo/lysosomal escape ability to MSNs, which augmented cytosolic delivery of an anticancer drug. Partial carboxylation of chitosan coated on MSNs allowed for a greater release of drug in a shorter duration of time while retaining pH-responsiveness and endo/lysosomal escape ability. Overall, the coating of carboxylated-chitosan over MSNs enabled tunable drug release kinetics, conjugation of aptamers (targeting agents), and endo/lysosomal escape which together significantly enhanced the efficacy of the developed drug delivery system., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

As pharmaceutical excipients, mesoporous silica nanoparticles (MSNs) have attracted considerable concern based on potential risks to the public. The impact of MSNs on biochemical metabolism is poorly understood, and few studies have compared the effects of MSNs administered via different routes. To evaluate the hepatotoxicity of MSNs, metabolomics, proteomics and transcriptomic analyses were performed in mice after intravenous (20 mg/kg/d) or oral ad-ministration (200 mg/kg/d) of MSNs for 10 days. Intravenous injection induced significant hepatic injury based on pathological inspection and increased the levels of AST/ALT and the inflammatory factors IL-6, IL-1β and TNF-a. Omics data suggested intravenous administration of MSNs perturbed the following metabolites: succinate, hypoxanthine, GSSG, NADP+, NADPH and 6-phosphogluconic acid. In addition, increases in GPX, SOD3, G6PD, HK, and PFK at proteomic and transcriptomic levels suggested elevation of glycolysis and pentose phosphate pathway, synthesis of glutathione and nucleotides, and antioxidative pathway activity, whereas oxidative phosphorylation, TCA and mitochondrial energy metabolism were reduced. On the other hand, oral administration of MSNs disturbed inflammatory factors and metabolites of ribose-5-phosphate, 6-phosphogluconate, GSSG, and NADP+ associated with the pentose phosphate pathway, glutathione synthesis and oxidative stress albeit to a lesser extent than intravenous injection despite the administration of a ten-fold greater dose. Overall, systematic biological data suggested that intravenous injection of nanoparticles of pharmaceutical excipients substantially affected hepatic metabolism function and induced oxidative stress and inflammation, whereas oral administration exhibited milder effects compared with intravenous injection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Sun, Xu and Wang.)

Purpose: Cancer vaccines are a promising therapeutic approach in cancer immunotherapy and can inhibit tumor growth and prevent tumor recurrence and metastasis by activating a sustained antitumor immunoprotective effect. However, the therapeutic effect of cancer vaccines is severely weakened by the low immunogenicity of cancer antigens and the immunosuppressive microenvironment in tumor tissues., Methods: Here, we report a novel hybrid membrane nanovaccine, composed of mesoporous silica nanoparticle as a delivery carrier, hybrid cell membranes obtained from dendritic cells and cancer cells, and R837 as an immune adjuvant (R837@HM-NPs). We investigated the anti-tumor, tumor recurrence and metastasis prevention abilities of R837@HM-NPs and their mechanisms of action through a series of in vivo and ex vivo experiments., Results: R837@HM-NPs not only provide effective antigenic stimulation but are also a durable supply of the immune adjuvant R837. In addition, R837@HM-NPs promote antigen endocytosis into dendritic cells via various receptor-mediated pathways. Compared with HM-NPs or R837@HM-NPs, R837@HM-NPs in combination with an immune checkpoint blockade showed stronger antitumor immune responses in inhibiting tumor growth, thus eliminating established tumors, and rejecting re-challenged tumors by regulating the immunosuppressive microenvironment and immunological memory effect., Conclusion: These findings suggest that the hybrid membrane nanovaccine in combination with immune checkpoint blockade is a powerful strategy to enhance antitumor immunotherapy without concerns of systemic toxicity., Competing Interests: The authors declare no financial or non-financial conflicts of interest for this work., (© 2022 Zhao et al.)

Systemic infections caused by life-threatening pathogens represent one of the main factors leading to clinical death. In this study, we developed a pathogen infection-responsive and macrophage endoplasmic reticulum-targeting nanoplatform to alleviate systemic infections. The nanoplatform is composed of large-pore mesoporous silica nanoparticles (MSNs) grafted by an endoplasmic reticulum-targeting peptide, and a pathogen infection-responsive cap containing the reactive oxygen species-cleavable boronobenzyl acid linker and bovine serum albumin. The capped MSNs exhibited the capacity to high-efficiently load the antimicrobial peptide melittin, and to rapidly release the cargo triggered by H 2 O 2 or the pathogen-macrophage interaction system, but had no obvious toxicity to macrophages. During the interaction with pathogenic Candida albicans cells and macrophages, the melittin-loading nanoplatform MSNE+MEL+TPB strongly inhibited pathogen growth, survived macrophages, and suppressed endoplasmic reticulum stress together with pro-inflammatory cytokine secretion. In a systemic infection model, the nanoplatform efficiently prevented kidney dysfunction, alleviated inflammatory symptoms, and protected the mice from death. This study developed a macrophage organelle-targeting nanoplatform for treatment of life-threatening systemic infections., Electronic Supplementary Material: Supplementary material (N 2 adsorption curves of the initial synthesized MSNs, FT-IR spectra of MSN, and MSNE, MEL release from the FITC-MEL-loading MSNE + TPB induced by different concentration of H 2 O 2 , viability of NIH3T3 cells, and DC2.4 cells after treatment of free MEL or the used nanoparticles, effect of MEL on C. albicans growth and macrophage death during the interaction between C. albicans and macrophages, effect of MEL and the nanoparticles on S. aureus growth and macrophage death during the interaction between S. aureus and macrophages, quantification of GRP78 (a) and activated Caspase-3, flow cytometry analysis of kidney non-macrophages with the Alexa Fluor 594 signal, survival curve of the infected mice treated by MEL or MSNE + MEL, kidney burden, blood urea levels and serum TNF-α levels in the infected mice) is available in the online version of this article at 10.1007/s12274-022-4211-z., (© Tsinghua University Press 2022.)

This study examines intra- and intercellular trafficking of mesoporous silica nanoparticles along microtubular highways, with an emphasis on intercellular bridges connecting interphase and telophase cells. The study of nanoparticle trafficking within and between cells during all phases of the cell cycle is relevant to payload destination and dilution, and impacts delivery of therapeutic or diagnostic agents. Super-resolution stochastic optical reconstruction and sub-airy unit image acquisition, the latter combined with Huygens deconvolution microscopy, enable single nanoparticle and microtubule resolution. Combined structural and functional data provide enhanced details on biological processes, with an example of mitotic inheritance during cancer cell trivision.

Mesoporous silica nanoparticles (MSNs) have been well-researched in the design and fabrication of advanced drug delivery systems (DDSs) due to their advantages such as good biocompatibility, large specific surface area and pore volume for drug loading, easily surface modification, adjusted size and good thermal/chemical stability. For MSN-based DDSs, gate materials are also necessary. And natural polysaccharides, one kind of the most abundant natural resource, have been widely applied as the "gatekeepers" in MSN-based DDSs. Polysaccharides are cheap and rich in sources with good biocompatibility, and some of them have important biological functions. In this review article, polysaccharides including chitosan, hyaluronic acid, sodium alginate and dextran, et al. are briefly introduced. And the preparation processes and properties such as controlled drug release, cancer targeting and disease diagnosis of functional polysaccharide/MSN-based DDSs are discussed., (Copyright © 2021 Elsevier B.V. All rights reserved.)