pH-responsive oxygen self-sufficient smart nanoplatform for enhanced tumor chemotherapy and photodynamic therapy.

Premature drug release in chemotherapy and hypoxic conditions in photodynamic therapy (PDT) are perplexing problems in tumor treatment. Thus, it is of great significance to develop the novel therapeutic system with controllable drug release and effective oxygen generation. Herein, a pH-responsive oxygen self-sufficient smart nanoplatform (named DHCCC), integrating hollow mesoporous silica nanoparticles (HMSNs), chitosan (CS), doxorubicin hydrochloride (DOX), chlorin e6 (Ce6) and catalase (CAT), is fabricated to enhance the tumor therapeutic efficacy efficiently through avoiding premature drug release and mitigating hypoxia of tumor microenvironment (TME). The drug DOX can be efficiently loaded into the HMSNs with large cavity and be controllable released because of the pH responsiveness of CS to the weak acidic TME, thereby elevating the chemotherapy efficacy. Meanwhile, CAT can catalyze the decomposition of endogenous hydrogen peroxide in situ generating oxygen to alleviate the hypoxia and enhance the PDT efficiency considerably. In vitro and in vivo results demonstrate that the combined chemo-photodynamic therapy based on the DHCCC nanoplatform exerts more effective antitumor efficacy than chemotherapy or PDT alone. The current study provides a promising inspiration to construct the pH-responsive oxygen self-sufficient smart nanomedicine with potentials to prevent premature drug leakage and overcome hypoxia for efficient tumor therapy.

Logic "AND Gate Circuit" Based Mussel Inspired Polydopamine Nanocomposite as Bioactive Antioxidant for Management of Oxidative Stress and Neurogenesis in Traumatic Brain Injury.

In the intricate landscape of Traumatic Brain Injury (TBI), the management of TBI remains a challenging task due to the extremely complex pathophysiological conditions and excessive release of reactive oxygen species (ROS) at the injury site and the limited regenerative capacities of the central nervous system (CNS). Existing pharmaceutical interventions are limited in their ability to efficiently cross the blood-brain barrier (BBB) and expeditiously target areas of brain inflammation. In response to these challenges herein, we designed novel mussel inspired polydopamine (PDA)-coated mesoporous silica nanoparticles (PDA-AMSNs) with excellent antioxidative ability to deliver a new potential therapeutic GSK-3ß inhibitor lead small molecule abbreviated as Neuro Chemical Modulator (NCM) at the TBI site using a neuroprotective peptide hydrogel (PANAP). PDA-AMSNs loaded with NCM (i.e., PDA-AMSN-D) into the matrix of PANAP were injected into the damaged area in an in vivo cryogenic brain injury model (CBI). This approach is specifically built while keeping the logic AND gate circuit as the primary focus. Where NCM and PDA-AMSNs act as two input signals and neurological functional recovery as a single output. Therapeutically, PDA-AMSN-D significantly decreased infarct volume, enhanced neurogenesis, rejuvenated BBB senescence, and accelerated neurological function recovery in a CBI.

Ultrasonic Preparation of Nano-CaCO3 Templates and Hollow Mesoporous SiO2 Nanoparticles for Voriconazole Loading.

CaCO3 nanoparticles (nano-CaCO3) as nano-templates were prepared using CaCl2 and Na2CO3 solutions under controlled sonication (19.5 kHz). Using the same ultrasonic device, subsequently, hollow mesoporous silica nanoparticles (HMSNs) were obtained by the hard template of nano-CaCO3. HMSNs were selected as carriers for the antifungal drug voriconazole (VOR) loading to overcome poor water solubility. Three-dimensional CaCO3 nanosheets HMSNs were obtained under gentle sonication. Three-dimensional CaCO3 nanosheets of 24.5 nm (hydrodynamic diameter) were obtained under 17.6 W for 3 min. HMSNs were synthesized by double-template method with nano-CaCO3 as the hard template. Transmission electron microscopy measurements showed that the prepared HMSNs possess hollow structures with particle size between 110 and 120 nm. Nitrogen physisorption at -196 °C revealed that the HMSNs had high surface area (401.57 m2/g), high pore volume (0.11 cm3/g), and uniform pore size (2.22 nm) that facilitated the effective encapsulation of VOR in the HMSNs. The loading capacity of VOR (wt%) on the HMSNs was 7.96%, and the total VOR release amount of VOR-HMSNs material was 71.40% at 480 min. The kinetic model confirmed that the release mechanism of HMSNs nanoparticles followed Fickian diffusion at pH = 7.4 and 37 °C. Moreover, the cumulative VOR release at 42 °C (86.05%) was higher than that at 37 °C (71.40%). The cumulative release amount of VOR from the VOR-HMSNs material was 92.37% at pH = 5.8 at the same temperature. Both nano-CaCO3 templates and HMSNs were prepared by sonication at 19.5 kHz. The as-prepared HMSNs can effectively encapsulate VOR and released drug by Fickian diffusion.

A Single-Dose mRNA Vaccine Employing Porous Silica Nanoparticles Induces Robust Immune Responses Against the Zika Virus.

Recently, lipid nanoparticles (LNPs)-based mRNA delivery has been approved by the FDA for SARS-CoV-2 vaccines. However, there are still considerable points for improvement in LNPs. Especially, local administration of LNPs-formulated mRNA can cause off-target translation of mRNA in distal organs which can induce unintended adverse effects. With the hypothesis that large and rigid nanoparticles can be applied to enhance retention of nanoparticles at the injection site, a polyethyleneimine (PEI)-coated porous silica nanoparticles (PPSNs)-based mRNA delivery platform is designed. PPSNs not only facilitate localized translation of mRNA at the site of injection but also prolonged protein expression. It is further demonstrated that the development of a highly efficacious Zika virus (ZIKV) vaccine using mRNA encoding full-length ZIKV pre-membrane (prM) and envelope (E) protein delivered by PPSNs. The ZIKV prME mRNA-loaded PPSNs vaccine elicits robust immune responses, including high levels of neutralizing antibodies and ZIKV E-specific T cell responses in C57BL/6 mice. Moreover, a single injection of prME-PPSNs vaccine provided complete protection against the ZIKV challenge in mice.

pH-responsive chitosan-mediated spherical mesoporous silica microspheres for high loading and controlled delivery of 5-Fluorouracil.

The objective of this study is to develop a drug carrier to overcome the inherent drawbacks of 5-Fluorouracil (5-Fu), including low bioavailability, short half-life, and systemic toxicity. In the present work, mesoporous silica nanoparticles (MSNs) capped by chitosan (CS) to encapsulate 5-Fu (5-Fu MSNs/CS) were fabricated by the sol-gel process, ultrasonic impregnation, and emulsion cross-linking. The 5-Fu MSNs/CS microspheres exhibit pH-responsive drug release and remarkable drug encapsulation capacity, as well as perfect sphericity, high specific surface area (680.62 cm2/g), and uniform particle size (2.64 ± 0.05 µm). The drug-loading content and encapsulation efficiency are 14.12 ± 0.53 % and 82.21 ± 2.13 %, respectively. The cumulative release of 5-Fu from MSNs/CS microspheres is fast and sustained at pH 5.0 (89.56 ± 0.97 %) compared to that at pH 7.4 (57.88 ± 0.91 %) in 96 h, and it is Fickian diffusion controlled. In conclusion, the MSNs/CS microspheres prepared in this study could be potential carriers for 5-Fu delivery.

Engineered Mesoporous Silica-Based Nanoparticles: Characterization of Surface Properties.

Mesoporous silica-based nanomaterials have emerged as multifunctional platforms with applications spanning catalysis, medicine, and nanotechnology. Since their synthesis in the early 1990s, these materials have attracted considerable interest due to their unique properties, including high surface area, tunable pore size, and customizable surface chemistry. This article explores the surface properties of a series of MSU-type mesoporous silica nanoparticles, elucidating the impact of different functionalization strategies on surface characteristics. Through an extensive characterization utilizing various techniques, such as FTIR, Z-potential, and nitrogen adsorption porosimetry, insights into the surface modifications of mesoporous silica nanoparticles are provided, contributing to a deeper understanding of their nanostructure and related interactions, and paving the way to possible unexpected actionability and potential applications.

Construction and synergistic anti-tumor study of a tumor microenvironment-based multifunctional nano-drug delivery system.

To solve the problems existing in the clinical application of hypericin (Hyp) and tirapazamine (TPZ), a nano-drug delivery system with synergistic anti-tumor functions was constructed using mesoporous silica nanoparticles (MSN) and sodium alginate (SA). The system exhibited excellent stability, physiological compatibility and targeted drug release performance in tumor tissues. In the in vitro and in vivo experiments, Hyp released from MSN killed tumor cells through photodynamic therapy (PDT). The degree of hypoxia in the tumor tissue site was exacerbated, enabling TPZ to fully exert its anti-tumor activity. Our studies suggested that the synergistic effects between the components of the nano-drug delivery system significantly improve the anti-tumor properties of Hyp and TPZ.

Involvement of miR-199a-5p-loaded mesoporous silica nanoparticle-polyethyleneimine-KALA in osteogenic differentiation.

Background/purpose: While there are numerous reports on surgical techniques and materials for bone grafting, limited methods are available to enhance the body's inherent capacity to heal bones. Here we investigated microRNA-199a (miR-199a), a molecular that promotes osteoblast differentiation and bone healing. Materials and methods: To construct a miR-199a delivery complex, miR-199a-5p mimics were coated with mesoporous silica nanoparticles (MSNs) following modified with polyethyleneimine (PEI) and peptide WEAKLAKALAKALAKHLAKALAKALKACEA (KALA) to obtain 199a-5p-loaded MSN-PEI-KALA. Nanoparticle complexes are assessed for particle size and zeta potential using transmission electron microscopy and dynamic light scattering. Then MC3T3-E1 cells are exposed to MSN_miR-199a-5p @PEI-KALA. The impact of MSN_miR-199a-5p@PEI-KALA at varying concentrations on cell viability is assessed using Cell Counting Kit-8. Cell uptake and distribution were analyzed by double fluorescent staining with fluorescein amidite-labeled MSN_miR-199a@PEI-KALA and lysosome labeling. On day 7 after osteogenic induction, alkaline phosphatase (ALP) staining was conducted. Results: The findings indicated that the nanoparticle complexes encapsulating PEI and peptide exhibited an augmentation in both particle size and zeta potential. At a dosage of 10 µg/mL, MSN_miR-199a@PEI-KALA displayed the lowest cytotoxicity compared to the control group. MC3T3-E1 cells treated with MSN_miR-199a-5p@PEI-KALA exhibited intensified ALP staining and elevated mRNA expression levels of ALP, runt-related transcription factor 2, and osteopontin, suggesting the involvement of miR-199a-5p-loaded MSN-PEI-KALA in osteogenic differentiation. Conclusion: The successful construction of the delivering complex MSN_miR-199a@PEI-KALA in present research highlights the promise of this biomaterial carrier for the application of miRNAs in treating bone defects.

Biofuel cell-based self-powered immunosensor for detection of 17ß-estradiol by integrating the target-induced biofuel release and biogate immunoassay.

A novel biofuel cell (BFC)-based self-powered electrochemical immunosensing platform was developed by integrating the target-induced biofuel release and biogate immunoassay for ultrasensitive 17ß-estradiol (E2) detection. The carbon nanocages/gold nanoparticle composite was employed in the BFCs device as the electrode material, through which bilirubin oxidase and glucose oxidase were wired to form the biocathode and bioanode, respectively. Positively charged mesoporous silica nanoparticles (PMSN) were encapsulated with glucose molecules as biofuel and subsequently coated by the negatively charged AuNPs-labelled anti-E2 antibody (AuNPs-Ab) serving as a biogate. The biogate could be opened efficiently and the trapped glucose released once the target E2 was recognized and captured by AuNPs-Ab due to the decreased adhesion between the antigen-antibody complex and PMSN. Then, glucose oxidase oxidized the glucose to produce a large number of electrons, resulting in significantly increased open-circuit voltage (EOCV). Promisingly, the proposed BFC-based self-powered immunosensor demonstrated exceptional sensitivity for the detection of E2 in the concentration range from 1.0 pg mL-1 to 10.0 ng mL -1, with a detection limit of 0.32 pg mL-1 (S/N = 3). Furthermore, the prepared BFC-based self-powered homogeneous immunosensor showed significant potential for implementation as a viable prototype for a mobile and an on-site bioassay system in food and environmental safety applications.

Silica nanoparticle design for colorectal cancer treatment: Recent progress and clinical potential.

Colorectal cancer (CRC) is the third most common cancer worldwide and the second most common cause of cancer death. Nanotherapies are able to selectively target the delivery of cancer therapeutics, thus improving overall antitumor efficiency and reducing conventional chemotherapy side effects. Mesoporous silica nanoparticles (MSNs) have attracted the attention of many researchers due to their remarkable advantages and biosafety. We offer insights into the recent advances of MSNs in CRC treatment and their potential clinical application value.

pH-Responsive Mesoporous Silica Nanoparticles Loaded with Naringin for Targeted Osteoclast Inhibition and Bone Regeneration.

Background: It is well-established that osteoclast activity is significantly influenced by fluctuations in intracellular pH. Consequently, a pH-sensitive gated nano-drug delivery system represents a promising therapeutic approach to mitigate osteoclast overactivity. Our prior research indicated that naringin, a natural flavonoid, effectively mitigates osteoclast activity. However, naringin showed low oral availability and short half-life, which hinders its clinical application. We developed a drug delivery system wherein chitosan, as gatekeepers, coats mesoporous silica nanoparticles loaded with naringin (CS@MSNs-Naringin). However, the inhibitory effects of CS@MSNs-Naringin on osteoclasts and the underlying mechanisms remain unclear, warranting further research. Methods: First, we synthesized CS@MSNs-Naringin and conducted a comprehensive characterization. We also measured drug release rates in a pH gradient solution and verified its biosafety. Subsequently, we investigated the impact of CS@MSNs-Naringin on osteoclasts induced by bone marrow-derived macrophages, focusing on differentiation and bone resorption activity while exploring potential mechanisms. Finally, we established a rat model of bilateral critical-sized calvarial bone defects, in which CS@MSNs-Naringin was dispersed in GelMA hydrogel to achieve in situ drug delivery. We observed the ability of CS@MSNs-Naringin to promote bone regeneration and inhibit osteoclast activity in vivo. Results: CS@MSNs-Naringin exhibited high uniformity and dispersity, low cytotoxicity (concentration≤120 µg/mL), and significant pH sensitivity. In vitro, compared to Naringin and MSNs-Naringin, CS@MSNs-Naringin more effectively inhibited the formation and bone resorption activity of osteoclasts. This effect was accompanied by decreased phosphorylation of key factors in the NF-κB and MAPK signaling pathways, increased apoptosis levels, and a subsequent reduction in the production of osteoclast-specific genes and proteins. In vivo, CS@MSNs-Naringin outperformed Naringin and MSNs-Naringin, promoting new bone formation while inhibiting osteoclast activity to a greater extent. Conclusion: Our research suggested that CS@MSNs-Naringin exhibited the strikingly ability to anti-osteoclasts in vitro and in vivo, moreover promoted bone regeneration in the calvarial bone defect.

Biomimetic Trypsin-Responsive Structure-Bridged Mesoporous Organosilica Nanomedicine for Precise Treatment of Acute Pancreatitis.

Developing strategies to target injured pancreatic acinar cells (PACs) in conjunction with primary pathophysiology-specific pharmacological therapy presents a challenge in the management of acute pancreatitis (AP). We designed and synthesized a trypsin-cleavable organosilica precursor bridged by arginine-based amide bonds, leveraging trypsin's ability to selectively identify guanidino groups on arginine via Asp189 at the active S1 pocket and cleave the carboxy-terminal (C-terminal) amide bond via catalytic triads. The precursors were incorporated into the framework of mesoporous silica nanoparticles (MSNs) for encapsulating the membrane-permeable Ca2+ chelator BAPTA-AM with a high loading content (∼43.9%). Mesenchymal stem cell membrane coating and surface modification with PAC-targeting ligands endow MSNs with inflammation recruitment and precise PAC-targeting abilities, resulting in the highest distribution at 3 h in the pancreas with 4.7-fold more accumulation than that of naked MSNs. The outcomes transpired as follows: After bioinspired MSNs' skeleton biodegradation by prematurely and massively activated trypsin, BAPTA-AM was on-demand released in injured PACs, thereby effectively eliminating intracellular calcium overload (reduced Ca2+ level by 81.3%), restoring cellular redox status, blocking inflammatory cascades, and inhibiting cell necrosis by impeding the IκBα/NF-κB/TNF-α/IL-6 and CaMK-II/p-RIP3/p-MLKL/caspase-8,9 signaling pathways. In AP mice, a single dose of the formulation significantly restored pancreatic function (lipase and amylase reduced more by 60%) and improved the survival rate from 50 to 91.6%. The formulation offers a potentially effective strategy for clinical translation in AP treatment.

ROS-responsive charge reversal mesoporous silica nanoparticles as promising drug delivery system for neovascular retinal diseases.

Intravitreal injection of biodegradable implant drug carriers shows promise in reducing the injection frequency for neovascular retinal diseases. However, current intravitreal ocular devices have limitations in adjusting drug release rates for individual patients, thereby affecting treatment effectiveness. Accordingly, we developed mesoporous silica nanoparticles (MSNs) featuring a surface that reverse its charge in response to reactive oxygen species (ROS) for efficient delivery of humanin peptide (HN) to retinal epithelial cells (ARPE-19). The MSN core, designed with a pore size of 2.8 nm, ensures a high HN loading capacity 64.4% (w/w). We fine-tuned the external surface of the MSNs by incorporating 20% Acetyl-L-arginine (Ar) to create a partial positive charge, while 80% conjugated thioketal (TK) methoxy polyethylene glycol (mPEG) act as ROS gatekeeper. Ex vivo experiments using bovine eyes revealed the immobilization of Ar-MSNs-TK-PEG (mean zeta potential: 2 mV) in the negatively charged vitreous. However, oxidative stress reversed the surface charge to -25 mV by mPEG loss, facilitating the diffusion of the nanoparticles impeded with HN. In vitro studies showed that ARPE-19 cells effectively internalize HN-loaded Ar-MSNs-TK, subsequently releasing the peptide, which offered protection against oxidative stress-induced apoptosis, as evidenced by reduced TUNEL and caspase3 activation. The inhibition of retinal neovascularization was further validated in an in vivo oxygen-induced retinopathy (OIR) mouse model.

Silica nanoparticles triggered epithelial ferroptosis via miR-21-5p/GCLM signaling to contribute to fibrogenesis in the lungs.

The toxicity of silica nanoparticles (SiNPs) to lung is known. We previously demonstrated that exposure to SiNPs promoted pulmonary impairments, but the precise pathogenesis remains elucidated. Ferroptosis has now been identified as a unique form of oxidative cell death, but whether it participated in SiNPs-induced lung injury remains unclear. In this work, we established a rat model with sub-chronic inhalation exposure of SiNPs via intratracheal instillation, and conducted histopathological examination, iron detection, and ferroptosis-related lipid peroxidation and protein assays. Moreover, we evaluated the effect of SiNPs on epithelial ferroptosis, possible mechanisms using in vitro-cultured human bronchial epithelial cells (16HBE), and also assessed the ensuing impact on fibroblast activation for fibrogenesis. Consequently, fibrotic lesions occurred in the rat lungs, concomitantly by enhanced lipid peroxidation, iron overload, and ferroptosis. Consistently, the in vitro data showed SiNPs triggered oxidative stress and caused the accumulation of lipid peroxides, resulting in ferroptosis. Importantly, the mechanistic investigation revealed miR-21-5p as a key player in the epithelial ferroptotic process induced by SiNPs via targeting GCLM for GSH depletion. Of note, ferrostatin-1 could greatly suppress ferroptosis and alleviate epithelial injury and ensuing fibroblast activation by SiNPs. In conclusion, our findings first revealed SiNPs triggered epithelial ferroptosis through miR-21-5p/GCLM signaling and thereby promoted fibroblast activation for fibrotic lesions, and highlighted the therapeutic potential of inhibiting ferroptosis against lung impairments upon SiNPs exposure.

Development of elliptic core-shell nanoparticles with fluorinated surfactants for 19F MRI.

Perfluorocarbon-encapsulated silica nanoparticles possess attractive features such as biological inertness and favorable colloidal properties for bioimaging with fluorine magnetic resonance imaging (19F MRI). Herein, a series of elliptic shaped silica nanoparticles with perfluorocarbon liquid perfluoro-15-crown-5 ether as core (PFCE@SiO2) were synthesized using fluorinated surfactants N-(perfluorononylmethyl)-N,N,N-trimethylammonium chloride (C10-TAC) and N-(perfluoroheptylmethyl)-N,N,N-trimethylammonium chloride (C8-TAC). The nanoparticles are characterized to obtain elliptic core-shell structures. PFCE@SiO2 showed strong 19F NMR signals of the encapsulated PFCE, indicating the potential as a highly sensitive 19F MRI probe. These elliptic PFCE@SiO2 nanoparticles provide a new option of 19F MRI probe with a morphology different from conventional nanospheres.

Controlled Quercetin Release by Fluorescent Mesoporous Nanocarriers for Effective Anti-Adipogenesis.

Introduction: Quercetin (QUER), a flavonoid abundant in fruits and vegetables, is emerging as a promising alternative therapeutic agent for obesity treatment due to its antioxidant and anti-adipogenic properties. However, the clinical application of QUER is limited by its poor solubility, low bioavailability, and potential toxicity at high doses. To address these challenges, this study aims to develop an advanced drug delivery system using fluorescent mesoporous silica nanoparticles (FMSNs) coated with polydopamine (PDA) for the efficient and sustained delivery of QUER to inhibit adipogenesis. Methods: The research included the synthesis of PDA-coated FMSNs for encapsulation of QUER, characterization of their mesoporous structures, and systematic investigation of the release behavior of QUER. The DPPH assay was used to evaluate the sustained radical scavenging potential. Concentration-dependent effects on 3T3-L1 cell proliferation, cellular uptake and adipogenesis inhibition were investigated. Results: PDA-coated FMSNs exhibited well-aligned mesoporous structures. The DPPH assay confirmed the sustained radical scavenging potential, with FMSNs-QUER@PDA showing 53.92 ± 3.48% inhibition at 72 h, which was higher than FMSNs-QUER (44.66 ± 0.57%) and free QUER (43.37 ± 5.04%). Concentration-dependent effects on 3T3-L1 cells highlighted the enhanced efficacy of PDA-coated FMSNs for cellular uptake, with a 1.5-fold increase compared to uncoated FMSNs. Adipogenesis inhibition was also improved, with relative lipid accumulation of 44.6 ± 4.6%, 37.3 ± 4.6%, and 36.5 ± 7.3% at 2.5, 5, and 10 µM QUER concentrations, respectively. Conclusion: The study successfully developed a tailored drug delivery system, emphasizing sustained QUER release and enhanced therapeutic effects. FMSNs, especially when coated with PDA, exhibit promising properties for efficient QUER delivery, providing a comprehensive approach that integrates advanced drug delivery technology and therapeutic efficacy.

Silica nanoparticles containing nano-silver and chlorhexidine to suppress Porphyromonas gingivalis biofilm and modulate multispecies biofilms toward healthy tendency.

Objectives: This research first investigated the effect of mesoporous silica nanoparticles (nMS) carrying chlorhexidine and silver (nMS-nAg-Chx) on periodontitis-related biofilms. This study aimed to investigate (1) the antibacterial activity on Porphyromonas gingivalis (P. gingivalis) biofilm; (2) the suppressing effect on virulence of P. gingivalis biofilm; (3) the regulating effect on periodontitis-related multispecies biofilm. Methods: Silver nanoparticles (nAg) and chlorhexidine (Chx) were co-loaded into nMS to form nMS-nAg-Chx. Inhibitory zone test and minimum inhibitory concentration (MIC) against P. gingivalis were tested. Growth curves, crystal violet (CV) staining, live/dead staining and scanning electron microscopy (SEM) observation were performed. Biofilm virulence was assessed. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and Quantitative Real Time-PCR (qPCR) were performed to validate the activity and composition changes of multispecies biofilm (P. gingivalis, Streptococcus gordonii and Streptococcus sanguinis). Results: nMS-nAg-Chx inhibited P. gingivalis biofilm dose-dependently (p<0.05), with MIC of 18.75 µg/mL. There were fewer live bacteria, less biomass and less virulence in nMS-nAg-Chx groups (p<0.05). nMS-nAg-Chx inhibited and modified periodontitis-related biofilms. The proportion of pathogenic bacteria decreased from 16.08 to 1.07% and that of helpful bacteria increased from 82.65 to 94.31% in 25 µg/mL nMS-nAg-Chx group for 72 h. Conclusions: nMS-nAg-Chx inhibited P. gingivalis growth, decreased biofilm virulence and modulated periodontitis-related multispecies biofilms toward healthy tendency. pH-sensitive nMS-nAg-Chx inhibit the pathogens and regulate oral microecology, showing great potential in periodontitis adjunctive therapy.

Green and Abrasion-Resistant Superhydrophobic Coatings Constructed with Tung Oil/Carnauba Wax/Silica for Wood Surface.

As a renewable, environmentally friendly, natural, and organic material, wood has been receiving extensive attention from various industries. However, the hydrophilicity of wood significantly impacts the stability and durability of its products, which can be effectively addressed by constructing superhydrophobic coatings on the surface of wood. In this study, tung oil, carnauba wax, and silica nanoparticles were used to construct superhydrophobic coatings on hydrophilic wood surfaces by a facile two-step dip-coating method. The surface wettability and morphology of the coatings were analyzed by a contact angle meter and scanning electron microscope, respectively. The results suggest that the coating has a micron-nanosized two-tiered structure, and the contact angle of the coating is higher than 150° and the roll-off angle is lower than 10°. Sandpaper abrasion tests and UV diffuse reflectance spectra indicate that the coatings have excellent abrasion resistance and good transparency. In addition, the coated wood shows excellent self-cleaning and water resistance, which have great potential for applications in industry and furniture manufacturing.

Epithelium-derived exosomes promote silica nanoparticles-induced pulmonary fibroblast activation and collagen deposition via modulating fibrotic signaling pathways and their epigenetic regulations.

BACKGROUND: In the context of increasing exposure to silica nanoparticles (SiNPs) and ensuing respiratory health risks, emerging evidence has suggested that SiNPs can cause a series of pathological lung injuries, including fibrotic lesions. However, the underlying mediators in the lung fibrogenesis caused by SiNPs have not yet been elucidated. RESULTS: The in vivo investigation verified that long-term inhalation exposure to SiNPs induced fibroblast activation and collagen deposition in the rat lungs. In vitro, the uptake of exosomes derived from SiNPs-stimulated lung epithelial cells (BEAS-2B) by fibroblasts (MRC-5) enhanced its proliferation, adhesion, and activation. In particular, the mechanistic investigation revealed SiNPs stimulated an increase of epithelium-secreted exosomal miR-494-3p and thereby disrupted the TGF-ß/BMPR2/Smad pathway in fibroblasts via targeting bone morphogenetic protein receptor 2 (BMPR2), ultimately resulting in fibroblast activation and collagen deposition. Conversely, the inhibitor of exosomes, GW4869, can abolish the induction of upregulated miR-494-3p and fibroblast activation in MRC-5 cells by the SiNPs-treated supernatants of BEAS-2B. Besides, inhibiting miR-494-3p or overexpression of BMPR2 could ameliorate fibroblast activation by interfering with the TGF-ß/BMPR2/Smad pathway. CONCLUSIONS: Our data suggested pulmonary epithelium-derived exosomes serve an essential role in fibroblast activation and collagen deposition in the lungs upon SiNPs stimuli, in particular, attributing to exosomal miR-494-3p targeting BMPR2 to modulate TGF-ß/BMPR2/Smad pathway. Hence, strategies targeting exosomes could be a new avenue in developing therapeutics against lung injury elicited by SiNPs.

Fabrication and characterization of apremilast-loaded zinc oxide-mesoporous silica nanoparticles for psoriasis treatment.

Aim: The study was aimed to formulate and evaluate apremilast-loaded zinc oxide-mesoporous silica nanoparticles for treatment of psoriasis. Materials & methods: Mesoporous silica nanoparticles were prepared by using sol-gel method and evaluated for particle size, in vitro drug release, in vitro cytotoxicity study and in vivo pharmacodynamic study. Results: The synthesized mesoporous silica nanoparticles showed particle size of 319.9 ± 3.9 nm, with 24 ± 0.217% of loading capacity. In vitro cytotoxicity study on A-431 cell line showed increased anti-psoriatic activity of apremilast-loaded zinc oxide-mesoporous silica nanoparticles. In vivo pharmacodynamic study and histological studies showed improved efficacy of drug in imiquimod-induced psoriasis mice model. Conclusion: The apremilast-loaded zinc oxide-mesoporous silica nanoparticles showed improved therapeutic efficacy, suggesting that they are promising approach for topical treatment of psoriasis.

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