Advances in Nanotherapy for Targeting Senescent Cells.

Aging is an inevitable process in the human body, and cellular senescence refers to irreversible cell cycle arrest caused by external aging-promoting mechanisms. Moreover, as age increases, the accumulation of senescent cells limits both the health of the body and lifespan and even accelerates the occurrence and progression of age-related diseases. Therefore, it is crucial to delay the periodic irreversible arrest and continuous accumulation of senescent cells to address the issue of aging. The fundamental solution is targeted therapy focused on eliminating senescent cells or reducing the senescence-associated secretory phenotype. Over the past few decades, the remarkable development of nanomaterials has revolutionized clinical drug delivery pathways. Their unique optical, magnetic, and electrical properties effectively compensate for the shortcomings of traditional drugs, such as low stability and short half-life, thereby maximizing the bioavailability and minimizing the toxicity of drug delivery. This article provides an overview of how nanomedicine systems control drug release and achieve effective diagnosis. By presenting and analyzing recent advances in nanotherapy for targeting senescent cells, the underlying mechanisms of nanomedicine for senolytic and senomorphic therapy are clarified, providing great potential for targeting senescent cells.

Enhancing bone repair through improved angiogenesis and osteogenesis using mesoporous silica nanoparticle-loaded Konjac glucomannan-based interpenetrating network scaffolds.

We have fabricated and characterized novel bioactive nanocomposite interpenetrating polymer network (IPN) scaffolds to treat bone defects by loading mesoporous silica nanoparticles (MSNs) into blends of Konjac glucomannan, polyvinyl alcohol, and polycaprolactone. By loading MSNs, we developed a porous nanocomposite scaffold with mechanical strengths comparable to cancellous bone. In vitro cell culture studies proved the cytocompatibility of the nanocomposite scaffolds. RT-PCR studies confirmed that these scaffolds significantly upregulated major osteogenic markers. The in vivo chick chorioallantoic membrane (CAM) assay confirmed the proangiogenic activity of the nanocomposite IPN scaffolds. In vivo studies were performed using Wistar rats to evaluate the scaffolds' compatibility, osteogenic activity, and proangiogenic properties. Liver and renal function tests confirmed that these scaffolds were nontoxic. X-ray and µ-CT results show that the bone defects treated with the nanocomposite scaffolds healed at a much faster rate compared to the untreated control and those treated with IPN scaffolds. H&E and Masson's trichrome staining showed angiogenesis near the newly formed bone and the presence of early-stage connective tissues, fibroblasts, and osteoblasts in the defect region at 8 weeks after surgery. Hence, these advantageous physicochemical and biological properties confirm that the nanocomposite IPN scaffolds are ideal for treating bone defects.

New Approaches for Basophil Activation Tests Employing Dendrimeric Antigen-Silica Nanoparticle Composites.

In vitro cell activation through specific IgE bound to high-affinity receptors on the basophil surface is a widely used strategy for the evaluation of IgE-mediated immediate hypersensitivity reactions to betalactams. Cellular activation requires drug conjugation to a protein to form a large enough structure displaying a certain distance between haptens to allow the cross-linking of two IgE antibodies bound to the basophil's surface, triggering their degranulation. However, no information about the size and composition of these conjugates is available. Routine in vitro diagnosis using the basophil activation test uses free amoxicillin, which is assumed to conjugate to a carrier present in blood. To standardize the methodology, we propose the use of well-controlled and defined nanomaterials functionalized with amoxicilloyl. Silica nanoparticles decorated with PAMAM-dendrimer-amoxicilloyl conjugates (NpDeAXO) of different sizes and amoxicilloyl densities (50-300 µmol amoxicilloyl/gram nanoparticle) have been prepared and chemically characterized. Two methods of synthesis were performed to ensure reproducibility and stability. Their functional effect on basophils was measured using an in-house basophil activation test (BAT) that determines CD63+ or CD203chigh activation markers. It was observed that NpDeAXO nanocomposites are not only able to specifically activate basophils but also do so in a more effective way than free amoxicillin, pointing to a translational potential diagnosis.

Mesoporous silica nanoparticles: a versatile carrier platform in lung cancer management.

Mesoporous silica nanoparticles (MSNPs) are inorganic nanoparticles that have been comprehensively investigated and are intended to deliver therapeutic agents. MSNPs have revolutionized the therapy for various conditions, especially cancer and infectious diseases. In this article, the viability of MSNPs' administration for lung cancer therapy has been reviewed. However, certain challenges lay ahead in the successful translation such as toxicology, immunology, large-scale production, and regulatory matters have made it extremely difficult to translate such discoveries from the bench to the bedside. This review highlights recent developments, characteristics, mechanism of action and customization for targeted delivery. This review also covers the most recent data that sheds light on MSNPs' extraordinary therapeutic potential in fighting lung cancer as well as future hurdles.

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Highly functionalized pH-triggered supramolecular nanovalve for targeted cancer chemotherapy.

Chemotherapeutic drug delivery systems are commonly limited by their short half-lives, poor bioavailability, and unsuccessful targetability. Herein, pH-responsive hybrid NPs consist of benzimidazole-coated mesoporous silica nanoparticles (BZ-MSN) loaded with naturally occurring flavonoid quercetin (QUE-BZ-MSN). The NPs were further capped with beta-cyclodextrin (BCD) to obtain our desired BCD-QUE-BZMSN, with a zeta potential around 7.05 ± 2.37 mV and diameter about 115.2 ± 19.02 nm. The abundance of BZ onto the nanoparticles facilitates targeted quercetin chemotherapy against model lung and liver cancer cell lines. FTIR, EDX, and NMR analyses revealed evidence of possible surface functionalizations. Powder XRD analysis showed that our designed BCD-QUE-BZMSN formulation is amorphous in nature. The UV and SEM showed that our designed BCD-QUE-BZMSN has high drug entrapment efficiency and a nearly spherical morphology. In vitro, drug release assessments show controlled pH-dependent release profiles that could enhance the targeted chemotherapeutic response against mildly acidic regions in cancer cell lines. The obtained BCD-QUE-BZMSN nanovalve achieved significantly higher cytotoxic efficacy as compared to QUE alone, which was evaluated by in vitro cellular uptake against liver and lung cancer cell lines, and the cellular morphological ablation was further confirmed via inverted microscopy. The outcomes of the study imply that our designed BCD-QUE-BZMSN nanovalve is a potential carrier for cancer chemotherapeutics.

Prostate cancer chemotherapy by intratumoral administration of Docetaxel-Mesoporous silica nanomedicines.

Docetaxel (DTX) is a recommended treatment in patients with metastasic prostate cancer (PCa), despite its therapeutic efficacy is limited by strong systemic toxicity. However, in localized PCa, intratumoral (IT) administration of DTX could be an alternative to consider that may help to overcome the disadvantages of conventional intravenous (IV) therapy. In this context, we here present the first in vivo preclinical study of PCa therapy with nanomedicines of mesoporous silica nanoparticles (MSN) and DTX by IT injection over a xenograft mouse model bearing human prostate adenocarcinoma tumors. The efficacy and tolerability, the biodistribution and the histopathology after therapy have been investigated for the DTX nanomedicine and the free drug, and compared with the IV administration of DTX. The obtained results demonstrate that IT injection of DTX and DTX nanomedicines allows precise and selective therapy of non-metastatic PCa and minimize systemic diffusion of the drug, showing superior activity than IV route. This allows reducing the therapeutic dose by one order and widens substantially the therapeutic window for this drug. Furthermore, the use of DTX nanomedicines as IT injection promotes strong antitumor efficacy and drug accumulation at the tumor site, improving the results obtained with the free drug by the same route.

Intermittent lysis on a single paper-based device to extract exosomal nucleic acid biomarkers from biological samples for downstream analysis.

As the role of exosomes in physiological and pathological processes has been properly perceived, harvesting them and their internal components is critical for subsequent applications. This study is a debut of intermittent lysis, which has been integrated into a simple and easy-to-operate procedure on a single paper-based device to extract exosomal nucleic acid biomarkers for downstream analysis. Exosomes from biological samples were captured by anti-CD63-modified papers before being intermittently lysed by high-temperature, short-time treatment with double-distilled water to release their internal components. Exosomal nucleic acids were finally adsorbed by sol-gel silica for downstream analysis. Empirical trials not only revealed that sporadically dropping 95 °C ddH2O onto the anti-CD63-modified papers every 5 min for 6 times optimized the exosomal nucleic acids extracted by the anti-CD63 paper but also verified that the whole deployed procedure is applicable for point-of-care testing (POCT) in low-resource areas and for both in vitro (culture media) and in vivo (plasma and chronic lesion) samples. Importantly, downstream analysis of exosomal miR-21 extracted by the paper-based procedure integrated with this novel technique discovered that the content of exosomal miR-21 in chronic lesions related to their stages and the levels of exosomal carcinoembryonic antigen originated from colorectal cancer cells correlated to their exosomal miR-21.

Effectiveness and biochemical impact of ozone gas and silica nanoparticles on Culex pipiens (Diptera: Culicidae).

Culex pipiens (Diptera: Culicidae) is a vector of many serious human diseases, and its control by the heavy use of chemical insecticides has led to the evolution of insecticide resistance and high environmental risks. Many safe alternatives, such as ozone gas (O3) and silica nanoparticles (silica NPs) can reduce these risks. Therefore, O3 and silica NPs were applied to 3rd larval instars of Cx. pipiens at different concentrations (100, 200, and 400 ppm) for different exposure times (1, 2, 3, and 5 min for O3 and 24, 48, and 72 h for silica NPs). The activity of some vital antioxidant enzymes as well as scanning electron microscopy of the body surface were also investigated. A positive correlation was observed between larval mortality % and the tested concentrations of O3 and silica NPs. O3 was more effective than silica NPs, it resulted in 92% mortality at 400 ppm for a short exposure time (5 min). O3-exposed larvae exhibited a significant increase in glutathione peroxidase, glutathione S-transferase, and catalase activities as well as the total antioxidant capacity. Scanning electron microscopy showing disruptive effects on the body surface morphology of ozone and silica NPs treated larvae. These results provide evidence that O3 and silica NPs have the potential for use as alternative vector control tools against Cx. pipiens.

Dimercaprol-modified mesoporous silica nanoparticles for efficient removal of toxic mercury ions from aqueous solution.

A surface-modified mesoporous silica nanoparticle containing dimercaprol monomers was created utilizing the sol-gel condensation process, using tetraethyl orthosilicate (TEOS) as the silica source and poloxamer as the structure directing agent. To accomplish this synthesis, 3-glycidoxypropyl triethoxysilane (GPTS, 20 mol%) was incorporated into the silica walls during the sol-gel condensation process, along with TEOS. Furthermore, dimercaprol (DM) monomers were incorporated onto silica surfaces by a ring-opening reaction between GPTS epoxy groups, and dimercaprol hydroxyl groups. The prepared dimercaprol-modified silica adsorbent (MSN-DT NPs) material has been studied using a variety of instruments, including XRD, FT-IR, N2 adsorption-desorption, scanning electron microscopy (SEM), transmission electron microscopy (TEM), thermogravimetric (TG) analysis, and zeta potential analysis. The MSN-DT NPs material selectively adsorbs mercury ions, with a high adsorption amount of 125 mg/g and a removal capability of roughly ~ 90% from the original metal ion mixture comprising other competing metals such as Pb2+, Ni2+, Fe2+, and Zn2+. The MSN-DT NPs adsorbent shows recyclable qualities for up to five cycles when treated with an acidic aqueous solution (0.1 M HCl). As a result, the MSN-DT NPs adsorbent may be regenerated and reused up to five times without losing its adsorption effectiveness. The experimental findings showed that the MSN-DT NPs adsorbent may be employed to selectively remove hazardous Hg2+ ions from an aqueous solution.

Galactose Glycopolymer-Grafted Silica Nanoparticles: Synthesis and Binding Studies with Lectin.

Weak binding of carbohydrates with protein receptors possesses serious drawbacks in the advancement of therapeutics; however, the development of strategies for multipoint interactions between carbohydrates and protein can overcome these challenges. One such method is developed in this work where glycopolymer-grafted silica nanoparticles with a large number of carbohydrate units are prepared for the interactions with multiple binding sites of the protein. First, a glycomonomer, ß-d-galactose-hydroxyethyl methacrylate (ß-GEMA), was synthesized in a two-step process by coupling ß-d-galactose pentaacetate and hydroxyethyl methacrylate (HEMA), followed by deacetylation for the preparation of poly(ß-GEMA) glycopolymers (GPs). Further, the poly(ß-GEMA) chains were grafted onto the silica nanoparticle (SiNP) surface by utilizing the "grafting-from" strategy of surface-initiated reversible addition-fragmentation chain transfer (RAFT) polymerization to prepare p(ß-GEMA)-grafted SiNPs (GNPs). Five different chain lengths ranging from 10 to 40 kDa of the GPs and the GNPs were prepared, and various characterization techniques confirmed the formation of GPs and grafting of the GPs on the SiNP surface. The particle size of GNPs and the number of GPs grafted on the SiNP surface showed a strong dependence on the chain length of the GPs. Further, the GNPs were subjected to a binding study with ß-galactose-specific protein peanut agglutinin (PNA). A much stronger binding in the case of GNPs was observed with an association constant ∼320 times and ∼53 times than that of the monomeric methyl-ß-d-galactopyranoside and the GPs, respectively. Additionally, the binding of the PNA with GNPs and GPs was also studied with varying chain lengths to understand the effects of the chain length on the binding affinity. A clear increase in binding constants was observed in the case of GNPs with increasing chain length of grafted GPs, attributed to the enhanced enthalpic and entropic contributions. This work holds its uniqueness in these improved interactions between carbohydrates and proteins, which can be used for carbohydrate-based targeted therapeutics.

Enhancing Slurry Stability and Surface Flatness of Silicon Wafers through Organic Amine-Catalyzed Synthesis Silica Sol.

The stability of slurries used for chemical mechanical polishing (CMP) is a crucial concern in industrial chip production, influencing both the quality and cost-effectiveness of polishing fluids. In silicon wafer polishing, the conventional use of commercial neutral silica sol combined with organic bases often leads to slurry instability. To address this issue, this study proposes organic amines-specifically ethanolamine (MEA), ethylenediamine (EDA), and tetramethylammonium hydroxide (TMAOH)-as catalysts for synthesizing alkaline silica sol tailored for silicon wafer polishing fluids. Sol-gel experiments and zeta potential measurements demonstrate the efficacy of this approach in enhancing the stability of silica sol. The quantitative analysis of surface hydroxyl groups reveals a direct correlation between enhanced stability and increased hydroxyl content. The application of the alkaline silica sol in silicon wafer polishing fluids improves polishing rates and enhances surface flatness according to atomic force microscopy (AFM). In addition, electrochemical experiments validate the capability of this polishing solution to mitigate corrosion on silicon wafer surfaces. These findings hold significant implications for the advancement of chemical mechanical polishing techniques in the field of integrated circuit fabrication.

High Cellular Internalization of Virus-Like Mesoporous Silica Nanoparticles Enhances Adaptive Antigen-Specific Immune Responses against Cancer.

Effective activation of an antigen-specific immune response hinges upon the intracellular delivery of cancer antigens to antigen-presenting cells (APCs), marking the initial stride in cancer vaccine development. Leveraging biomimetic topological morphology, we employed virus-like mesoporous silica nanoparticles (VMSNs) coloaded with antigens and toll-like receptor 9 (TLR9) agonists to craft a potent cancer vaccine. Our VMSNs could be efficiently internalized by APCs to a greater extent than their nonviral structured counterparts, thereby promoting the activation of APCs by upregulating the TLR9 pathway and cross-presenting ovalbumin (OVA) epitopes. In in vivo animal study, VMSN-based nanovaccines triggered substantial CD4+ and CD8+ lymphocyte populations in both lymph nodes and spleen while inducing the effector memory of adaptive T cells. Consequently, VMSN-based nanovaccines suppressed tumor progression and increased the survival rate of B16-OVA-bearing mice in both prophylactic and therapeutic studies. The combination of immune checkpoint blockade (ICB) with the VMSN-based nanovaccine has synergistic effects in significantly preventing tumor progression under therapeutic conditions. These findings highlight the potential of viral structure-mimicking mesoporous silica nanoparticles as promising candidates for antigen-delivering nanocarriers in vaccine development.

Interfacial Rheological Investigation of Modified Silica Nanoparticles with Different Alkyl Chain Lengths at the n-Octane/Water Interface.

The interfacial dilational rheology of silica nanoparticles (NPs) directly reflects the relationship between surface structure and interfacial behaviors in NPs, which has attracted significant attention in various industrial fields. In this work, modified silica nanoparticles (MNPs) with various alkyl chain lengths were synthesized and systematically characterized using Fourier transform infrared spectra, Zeta potential, and water contact angle measurements. It was found that the MNPs were successfully fabricated with similar degrees of modification. Subsequently, the interfacial behaviors of the MNPs in an n-octane/water system were investigated through interfacial dilational rheological experiments. The length of the modified alkyl chain dominated the hydrophilic-lipophile balance and the interfacial activity of the MNPs, evaluated by the equilibrium interfacial tension (IFT) variation and dilational elasticity modulus. In the large amplitude compression experiment, the balance between the electrostatic repulsion and interfacial activity in the MNPs was responsible for their ordered interfacial arrangement. The MNPs with the hexyl alkyl chain (M6C) presented the optimal amphipathy and could partly overcome the repulsion, causing a dramatic change in surface pressure. This was further confirmed by the variations in IFT and dilational elasticity during the compression path. The study provides novel insights into the interfacial rheology and interactions of functionally modified NPs.

Biodegradable silica nanoparticles for efficient linear DNA gene delivery.

Targeting, safety, scalability, and storage stability of vectors are still challenges in the field of nucleic acid delivery for gene therapy. Silica-based nanoparticles have been widely studied as gene carriers, exhibiting key features such as biocompatibility, simplistic synthesis, and enabling easy surface modifications for targeting. However, the ability of the formulation to incorporate DNA is limited, which restricts the number of DNA molecules that can be incorporated into the particle, thereby reducing gene expression. Here we use polymerase chain reaction (PCR)-generated linear DNA molecules to augment the coding sequences of gene-carrying nanoparticles, thereby maximizing nucleic acid loading and minimizing the size of these nanocarriers. This approach results in a remarkable 16-fold increase in protein expression six days post-transfection in cells transfected with particles carrying the linear DNA compared with particles bearing circular plasmid DNA. The study also showed that the use of linear DNA entrapped in DNA@SiO2 resulted in a much more efficient level of gene expression compared to standard transfection reagents. The system developed in this study features simplicity, scalability, and increased transfection efficiency and gene expression over existing approaches, enabled by improved embedment capabilities for linear DNA, compared to conventional methods such as lipids or polymers, which generally show greater transfection efficiency with plasmid DNA. Therefore, this novel methodology can find applications not only in gene therapy but also in research settings for high-throughput gene expression screenings.

Surface-modified, zinc-incorporated mesoporous silica nanoparticles with improved antibacterial and rapid hemostatic properties.

Severe bleeding and bacterial infections pose significant challenges to the global public health. Effective hemostatic materials have the potential to be used for rapid control of bleeding at the wound site. In this study, mesoporous silica nanoparticles (MSN) were doped with zinc ions (MSN@Zn) and subsequently functionalized with carboxyl (-COOH) groups through post-grafting, resulting in (MSN@Zn-COOH). The results demonstrated the successful functionalization of carboxyl groups on the surface of MSN@Zn mesoporous materials with minimal impact on the morphology. The released zinc ions showed potent antibacterial activity (above ∼80 %) against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). In vitro and in vivo assessments of MSN@Zn-COOH revealed excellent hemostatic effects and favorable blood compatibility. Hemolysis percentages associated with MSN@Zn-COOH exhibited noteworthy reductions in comparison to MSN. Furthermore, a decrease in APTT (a test evaluating the intrinsic coagulation pathway) of modified MSN@Zn indicated enhanced hemostasis, supported by their negative zeta potential (∼ -14 to -43 mV). Importantly, all samples showed no cytotoxicity. This work underscores the potential of MSN@Zn-COOH, with its combined hemostatic performance and antibacterial activity, for emergency clinical applications.

Dual-Functionalized Mesoporous Silica Nanoparticles for Celecoxib Delivery: Amine Grafting and Imidazolyl PEI Gatekeepers for Enhanced Loading and Controlled Release with Reduced Toxicity.

The development of targeted drug delivery systems has been a pivotal area in nanomedicine, addressing challenges like low drug loading capacity, uncontrolled release, and systemic toxicity. This study aims to develop and evaluate dual-functionalized mesoporous silica nanoparticles (MSN) for targeted delivery of celecoxib, enhancing drug loading, achieving controlled release, and reducing systemic toxicity through amine grafting and imidazolyl polyethyleneimine (PEI) gatekeepers. MSN were synthesized using the sol-gel method and functionalized with (3-aminopropyl) triethoxysilane (APTES) to create amine-grafted MSN (MSN-NH2). Celecoxib was loaded into MSN-NH2, followed by conjugation of imidazole-functionalized PEI (IP) gatekeepers synthesized via carbodiimide coupling. Characterization was conducted using Fourier-transform infrared spectroscopy (FTIR) and proton nuclear magnetic resonance (1H-NMR). Drug loading capacity, entrapment efficiency, and in vitro drug release at pH 5.5 and 7.4 were evaluated. Cytotoxicity was assessed using the MTT assay on RAW 264.7 macrophages. The synthesized IP was confirmed by FTIR and 1H-NMR. Amine-grafted MSN demonstrated a celecoxib loading capacity of 12.91 ± 2.02%, 2.1 times higher than non-functionalized MSN. In vitro release studies showed pH-responsive behavior with significantly higher celecoxib release from MSN-NH2-celecoxib-IP at pH 5.5 compared to pH 7.4, achieving a 33% increase in release rate within 2 h. Cytotoxicity tests indicated significantly higher cell viability for IP-treated cells compared to PEI-treated cells, confirming reduced toxicity. The dual-functionalization of MSN with amine grafting and imidazolyl PEI gatekeepers enhances celecoxib loading and provides controlled pH-responsive drug release while reducing systemic toxicity. These findings highlight the potential of this advanced drug delivery system for targeted anti-inflammatory and anticancer therapies.

Hybrid Nanoparticles Based on Mesoporous Silica and Functionalized Biopolymers as Drug Carriers for Chemotherapeutic Agents.

Mesoporous silica nanoparticles (MSNs) are promising drug carriers for cancer therapy. Their functionalization with ligands for specific tissue/cell targeting and stimuli-responsive cap materials for sealing drugs within the pores of MSNs is extensively studied for biomedical and pharmaceutical applications. The objective of the present work was to establish MSNs as ideal nanocarriers of anticancer drugs such as 5-FU and silymarin by exploiting characteristics such as their large surface area, pore size, and biocompatibility. Furthermore, coating with various biopolymeric materials such as carboxymethyl chitosan-dopamine and hyaluronic acid-folic acid on their surface would allow them to play the role of ligands in the process of active targeting to tumor cells in which there is an overexpression of specific receptors for them. From the results obtained, it emerged, in fact, that these hybrid nanoparticles not only inhibit the growth of glioblastoma and breast cancer cells, but also act as pH-responsive release systems potentially useful as release vectors in tumor environments.

Silica nanoparticles induce liver lipid metabolism disorder via ACSL4-mediated ferroptosis.

The disease burden of non-alcoholic fatty liver disease (NAFLD) is increasing worldwide. Emerging evidence has revealed that silica nanoparticles (SiNPs) could disorder the liver lipid metabolism and cause hepatotoxicity, but the underlying mechanism remains unknown. The purpose of this study is to elucidate the molecular mechanism of hepatic lipid metabolism disorder caused by SiNPs, and to reveal the role of ferroptosis in SiNPs-induced hepatotoxicity. To explore the phenotypic changes in liver, the wild-type C57BL/6J mice were exposed to different doses of SiNPs (5, 10, 20 mg/kg·bw) with or without melatonin (20 mg/kg·bw). SiNPs accelerated hepatic oxidative stress and promoted pathological injury and lipid accumulation, resulting in NAFLD development. Melatonin significantly inhibited the oxidative damage caused by SiNPs. Then, the hepatocytes were treated with SiNPs, the ferroptosis inducer and inhibitor, respectively. In vitro, SiNPs (25 µg/mL) generated mitochondrial and intracellular Fe2+ accumulation and lipid peroxidation repair ability impairment, decreased the activity of GPX4 through ACSL4/p38 MAPK signaling pathway, resulting in ferroptosis of hepatocytes. Notably, Erastin (the ferroptosis activator, 5 µM) increased the sensitivity of hepatocytes to ferroptosis. Ferrostatin-1 (Fer-1, the ferroptosis inhibitor, 5 µM) restored GPX4 activity and protected against deterioration of lipid hydroperoxides (LOOHs) to salvage SiNPs-induced cytotoxicity. Finally, the liver tissue conditional ACSL4 knockout (cKO) mice and ACSL4-KO hepatocytes were adopted to further identify the role of the ACSL4-mediated ferroptosis on SiNPs-induced NAFLD development. The results displayed ACSL4 knockout could down-regulate the lipid peroxidation and ferroptosis, ultimately rescuing the progression of NAFLD. In summary, our data indicated that ACSL4/p38 MAPK/GPX4-mediated ferroptosis was a novel and critical mechanism of SiNPs-induced NAFLD.

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.

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.