Magnetically modified-mitoxantrone mesoporous organosilica drugs: an emergent multimodal nanochemotherapy for breast cancer.

BACKGROUND: Chemotherapy, the mainstay treatment for metastatic cancer, presents serious side effects due to off-target exposure. In addition to the negative impact on patients' quality of life, side effects limit the dose that can be administered and thus the efficacy of the drug. Encapsulation of chemotherapeutic drugs in nanocarriers is a promising strategy to mitigate these issues. However, avoiding premature drug release from the nanocarriers and selectively targeting the tumour remains a challenge. RESULTS: In this study, we present a pioneering method for drug integration into nanoparticles known as mesoporous organosilica drugs (MODs), a distinctive variant of periodic mesoporous organosilica nanoparticles (PMOs) in which the drug is an inherent component of the silica nanoparticle structure. This groundbreaking approach involves the chemical modification of drugs to produce bis-organosilane prodrugs, which act as silica precursors for MOD synthesis. Mitoxantrone (MTO), a drug used to treat metastatic breast cancer, was selected for the development of MTO@MOD nanomedicines, which demonstrated a significant reduction in breast cancer cell viability. Several MODs with different amounts of MTO were synthesised and found to be efficient nanoplatforms for the sustained delivery of MTO after biodegradation. In addition, Fe3O4 NPs were incorporated into the MODs to generate magnetic MODs to actively target the tumour and further enhance drug efficacy. Importantly, magnetic MTO@MODs underwent a Fenton reaction, which increased cancer cell death twofold compared to non-magnetic MODs. CONCLUSIONS: A new PMO-based material, MOD nanomedicines, was synthesised using the chemotherapeutic drug MTO as a silica precursor. MTO@MOD nanomedicines demonstrated their efficacy in significantly reducing the viability of breast cancer cells. In addition, we incorporated Fe3O4 into MODs to generate magnetic MODs for active tumour targeting and enhanced drug efficacy by ROS generation. These findings pave the way for the designing of silica-based multitherapeutic nanomedicines for cancer treatment with improved drug delivery, reduced side effects and enhanced efficacy.

Loading cinnamon oil into pH-sensitive chitosan grafted mesoporous silica nanoparticles via supercritical carbon dioxide.

Stimulus-responsive mesoporous silica nanoparticles (MSNs) have displayed great potentiality for controlled-release and targeted drug delivery. In the current work, a supercritical fluid method was utilized to successfully prepare cinnamon oil loaded into chitosan grafted MSNs (CO@CS-MSNs). The influencing factors of drug loads, such as pressure, temperature, impregnation time and depressure time, were investigated. The structure of CO@CS-MSNs was demonstrated with Fourier-transform infrared (FT-IR) spectroscopy, transmission electron microscope (TEM), scanning electron microscopy (SEM), thermogravimetry (TG) as well as X-ray diffraction (XRD). The drug release assays in vitro at various pH conditions displayed that CO@CS-MSNs had an excellent pH-responsive release behavior, which confirmed that CO was loaded successfully into the CO@CS-MSNs. The findings indicated that the supercritical fluid approach is a non-destructive and efficient approach for stimulus-responsive MSNs, which is expected to further expand its application range.

Targeting c-Myc with decoy oligodeoxynucleotide-loaded polycationic nanoparticles inhibits cell growth and induces apoptosis in cancer stem-like cells (NTERA-2).

BACKGROUND: An increase in cancer stem cell (CSC) populations and their resistance to common treatments could be a result of c-Myc dysregulations in certain cancer cells. In the current study, we investigated anticancer effects of c-Myc decoy ODNs loaded-poly (methacrylic acid-co-diallyl dimethyl ammonium chloride) (PMA-DDA)-coated silica nanoparticles as carriers on cancer-like stem cells (NTERA-2). METHODS AND RESULTS: The physicochemical characteristics of the synthesized nanocomposites (SiO2@PMA-DDA-DEC) were analyzed using FT-IR, DLS, and SEM techniques. UV-Vis spectrophotometer was applied to analyze the release pattern of decoy ODNs from the nanocomposite. Furthermore, uptake, cell viability, apoptosis, and cell cycle assays were used to investigate the anticancer effects of nanocomposites loaded with c-Myc decoy ODNs on NTERA-2 cancer cells. The results of physicochemical analytics demonstrated that SiO2@PMA-DDA-DEC nanocomposites were successfully synthesized. The prepared nanocomposites were taken up by NTERA-2 cells with high efficiency, and could effectively inhibit cell growth and increase apoptosis rate in the treated cells compared to the control group. Moreover, SiO2@PMA-DDA nanocomposites loaded with c-Myc decoy ODNs induced cell cycle arrest at the G0/G1 phase in the treated cells. CONCLUSIONS: The conclusion drawn from this study is that c-Myc decoy ODN-loaded SiO2@PMA-DDA nanocomposites can effectively inhibit cell growth and induce apoptosis in NTERA-2 cancer cells. Moreover, given that a metal core is incorporated into this synthetic nanocomposite, it could potentially be used in conjunction with irradiation as part of a decoy-radiotherapy combinational therapy in future investigations.

Progressive enhanced photodynamic therapy and enhanced chemotherapy fighting against malignant tumors with sequential drug release.

During the process of malignant tumor treatment, photodynamic therapy (PDT) exerts poor efficacy due to the hypoxic environment of the tumor cells, and long-time chemotherapy reduces the sensitivity of tumor cells to chemotherapy drugs due to the presence of drug-resistant proteins on the cell membranes for drug outward transportation. Therefore, we reported a nano platform based on mesoporous silica coated with polydopamine (MSN@PDA) loading PDT enhancer MnO2, photosensitizer indocyanine green (ICG) and chemotherapeutic drug doxorubicin (DOX) (designated as DMPIM) to achieve a sequential release of different drugs to enhance treatment of malignant tumors. MSN was first synthesized by a template method, then DOX was loaded into the mesoporous channels of MSN, and locked by the PDA coating. Next, ICG was modified by π-π stacking on PDA, and finally, MnO2layer was accumulated on the surface of DOX@MSN@PDA- ICG@MnO2, achieving orthogonal loading and sequential release of different drugs. DMPIM first generated oxygen (O2) through the reaction between MnO2and H2O2after entering tumor cells, alleviating the hypoxic environment of tumors and enhancing the PDT effect of sequentially released ICG. Afterwards, ICG reacted with O2in tumor tissue to produce reactive oxygen species, promoting lysosomal escape of drugs and inactivation of p-glycoprotein (p-gp) on tumor cell membranes. DOX loaded in the MSN channels exhibited a delay of approximately 8 h after ICG release to exert the enhanced chemotherapy effect. The drug delivery system achieved effective sequential release and multimodal combination therapy, which achieved ideal therapeutic effects on malignant tumors. This work offers a route to a sequential drug release for advancing the treatment of malignant tumors.

Synthetic silica fibers of different length, diameter and shape: synthesis and interaction with rat (NR8383) and human (THP-1) macrophages in vitro, including chemotaxis and gene expression profile.

BACKGROUND: Inhalation of biopersistent fibers like asbestos can cause strong chronic inflammatory effects, often resulting in fibrosis or even cancer. The interplay between fiber shape, fiber size and the resulting biological effects is still poorly understood due to the lack of reference materials. RESULTS: We investigated how length, diameter, aspect ratio, and shape of synthetic silica fibers influence inflammatory effects at doses up to 250 µg cm-2. Silica nanofibers were prepared with different diameter and shape. Straight (length ca. 6 to 8 µm, thickness ca. 0.25 to 0.35 µm, aspect ratio ca. 17:1 to 32:1) and curly fibers (length ca. 9 µm, thickness ca. 0.13 µm, radius of curvature ca. 0.5 µm, aspect ratio ca. 70:1) were dispersed in water with no apparent change in the fiber shape during up to 28 days. Upon immersion in aqueous saline (DPBS), the fibers released about 5 wt% silica after 7 days irrespectively of their shape. The uptake of the fibers by macrophages (human THP-1 and rat NR8383) was studied by scanning electron microscopy and confocal laser scanning microscopy. Some fibers were completely taken up whereas others were only partially internalized, leading to visual damage of the cell wall. The biological effects were assessed by determining cell toxicity, particle-induced chemotaxis, and the induction of gene expression of inflammatory mediators. CONCLUSIONS: Straight fibers were only slightly cytotoxic and caused weak cell migration, regardless of their thickness, while the curly fibers were more toxic and caused significantly stronger chemotaxis. Curly fibers also had the strongest effect on the expression of cytokines and chemokines. This may be due to the different aspect ratio or its twisted shape.

PNA-Functionalized, Silica Nanowires-Filled Glass Microtube for Ultrasensitive and Label-Free Detection of miRNA-21.

MicroRNAs (miRNAs) are endogenous and noncoding single-stranded RNA molecules with a length of approximately 18-25 nucleotides, which play an undeniable role in early cancer screening. Therefore, it is very important to develop an ultrasensitive and highly specific method for detecting miRNAs. Here, we present a bottom-up assembly approach for modifying glass microtubes with silica nanowires (SiNWs) and develop a label-free sensing platform for miRNA-21 detection. The three-dimensional (3D) networks formed by SiNWs make them abundant and highly accessible sites for binding with peptide nucleic acid (PNA). As a receptor, PNA has no phosphate groups and exhibits an overall electrically neutral state, resulting in a relatively small repulsion between PNA and RNA, which can improve the hybridization efficiency. The SiNWs-filled glass microtube (SiNWs@GMT) sensor enables ultrasensitive, label-free detection of miRNA-21 with a detection limit as low as 1 aM at a detection range of 1 aM-100 nM. Noteworthy, the sensor can still detect miRNA-21 in the range of 102-108 fM in complex solutions containing 1000-fold homologous interference of miRNAs. The high anti-interference performance of the sensor enables it to specifically recognize target miRNA-21 in the presence of other miRNAs and distinguish 1-, 3-mismatch nucleotide sequences. Significantly, the sensor platform is able to detect miRNA-21 in the lysate of breast cancer cell lines (e.g., MCF-7 cells and MDA-MB-231 cells), indicating that it has good potential in the screening of early breast cancers.

Biogated mesoporous silica nanoagents for inhibition of cell migration and combined cancer therapy.

Migration is an initial step in tumor expansion and metastasis; suppressing cellular migration is beneficial to cancer therapy. Herein, we designed a novel biogated nanoagents that integrated the migration inhibitory factor into the mesoporous silica nanoparticle (MSN) drug delivery nanosystem to realize cell migratory inhibition and synergistic treatment. Antisense oligonucleotides (Anti) of microRNA-330-3p, which is positively related with cancer cell proliferation, migration, invasion, and angiogenesis, not only acted as the locker for blocking drugs but also acted as the inhibitory factor for suppressing migration via gene therapy. Synergistic with gene therapy, the biogated nanoagents (termed as MSNs-Gef-Anti) could achieve on-demand drug release based on the intracellular stimulus-recognition and effectively kill tumor cells. Experimental results synchronously demonstrated that the migration suppression ability of MSNs-Gef-Anti nanoagents (nearly 30%) significantly contributed to cancer therapy, and the lethality rate of the non-small-cell lung cancer was up to 70%. This strategy opens avenues for realizing efficacious cancer therapy and should provide an innovative way for pursuing the rational design of advanced nano-therapeutic platforms with the combination of cancer cell migratory inhibition.

Electrosprayable Levan-Coated Nanoclusters and Ultrasound-Responsive Drug Delivery for Cancer Therapy.

In this study, we synthesized levan shell hydrophobic silica nanoclusters encapsulating doxorubicin (L-HSi-Dox) and evaluated their potential as ultrasound-responsive drug delivery systems for cancer treatment. L-HSi-Dox nanoclusters were successfully fabricated by integrating a hydrophobic silica nanoparticle-doxorubicin complex as the core and an amphiphilic levan carbohydrate polymer as the shell by using an electrospray technique. Characterization analyses confirmed the stability, size, and composition of the nanoclusters. In particular, the nanoclusters exhibited a controlled release of Dox under aqueous conditions, demonstrating their potential as efficient drug carriers. The levanic groups of the nanoclusters enhanced the targeted delivery of Dox to specific cancer cells. Furthermore, the synergism between the nanoclusters and ultrasound effectively reduced cell viability and induced cell death, particularly in the GLUT5-overexpressing MDA-MB-231 cells. In a tumor xenograft mouse model, treatment with the nanoclusters and ultrasound significantly reduced the tumor volume and weight without affecting the body weight. Collectively, these results highlight the potential of the L-HSi-Dox nanoclusters and ultrasound as promising drug delivery systems with an enhanced therapeutic efficacy for biomedical applications.

In situ carbonization metamorphoses porous silica particles into biodegradable therapeutic carriers of lesser consequence on TGF-ß1 mediated fibrosis.

Extensive modifications have been made to the synthesis protocol for porous silica particles to improve the shape, size and yield percentage, but problems associated with improvement in biodegradability and decrease in chances to induce side effects still remain a concern. To circumvent these limitations, a facile modification strategy has been employed through in situ carbonization of porous silica particles. Herein, carbon particles were integrated within porous silica core-shell particles (Si-P-CNPs) during the synthesis process and found to preserve the ordered structural morphology. Curcumin was used as a model drug for loading in prepared Si-P-CNPs whereas lung cancer cells were used as a model system to study the in vitro fate. These Si-P-CNPs showed improved drug loading, drug effectivity, biodegradability and avoidance of interaction with transforming growth factor ß1 (TGF-ß1) indicating the possibility of reducing the chances of lung fibrosis and thereby enhancing the safety profile over conventional porous silica particles.

Vortex-assisted dispersive micro-solid-phase extraction using silica-supported Fe2O3-modified khat (Catha edulis) biochar nanocomposite followed by GC-MS for the determination of organochlorine pesticides in juice samples.

In this paper, dispersive micro-solid phase extraction technique was developed for the purpose of extracting and preconcentrating organochlorine pesticide residues in juice samples before their separation and quantitative analysis by gas chromatography-mass spectrometry. A sorbent composed of a silica-supported Fe2O3-modified khat leftover biochar nanocomposite (SiO2-Fe2O3-KLBNC) was implemented in the process. To improve the dispersion of the sorbent in the solution, vortex mixer was employed. Experimental parameters influencing the performance of the method were optimized, and the optimal conditions were established. With these conditions, linear dynamic ranges ranged from 0.003 to 100.0 ng/mL were achieved, with a correlation coefficient (r2) ≥ 0.9981. The limits of detection and quantification, determined by signal-to-noise ratios of 3 and 10, respectively, were found to be in the ranges of 0.001-0.006 ng/mL and 0.003-0.020 ng/mL. Intra- and inter-day precision, values ranging from 0.3-4.8% and 1.7-5.2% were obtained, respectively. The matrix-matched extraction recoveries demonstrated favorable outcomes, falling within the range of 83.4-108.3%. The utilization of khat leftover as an adsorbent in contemporary sample preparation methodologies offers a cost-effective alternative to the currently available, yet expensive, adsorbents. This renders it economically viable, particularly in resource-constrained regions, and is anticipated to witness widespread adoption in the coming future.

Ordered Mesoporous Silica Delivering siRNA as Cancer Nanotherapeutics: A Comprehensive Review.

Nanosized mesoporous silica has emerged as a promising flexible platform delivering siRNA for cancer treatment. This ordered mesoporous nanosized silica provides attractive features of well-defined and tunable porosity, structure, high payload, and multiple functionalizations for targeted delivery and increasing biocompatibility over other polymeric nanocarriers. Moreover, it also overcomes the lacunae associated with traditional administration of drugs. Chemically modified porous silica matrix efficiently entraps siRNA molecules and prevents their enzymatic degradation and premature release. This Review discusses the synthesis of silica using the sol-gel approach and the advantages with different silica mesostructure. Herein, the factors affecting the synthesis of silica at nanometer scale, shape, porosity and nanoparticle surface modification are also highlighted to attain the desired nanostructured silica carriers. Additional emphasis is given to chemically modified silica delivering siRNA, where the silica nanoparticle surface was modified with different chemical moieties such as amine modified with (3-aminoropyl) triethoxysilane, polyethylenimine, chitosan, poly(ethylene glycol), and cyclodextrin polymer modification to attain high therapeutic loading, improved dispersibility and biocompatibility. Upon systemic administration, ordered mesoporous nanosized silica encounters blood cells, immune cells, and organs mainly of the reticuloendothelial system (RES). Thereby, biocompatibility and biodistribution of silica based nanocarriers are deliberated to design principles for smart and efficacious nanostructured silica-siRNA carriers and their clinical trial status. This Review further reports the future scopes and challenges for developing silica nanomaterial as a promising siRNA delivery vehicle demanding FDA approval.

Double-layer hollow mesoporous silica nanoparticles for ultrasound-guided photodynamic treatment.

Cervical carcinoma persists as a major global public health burden. While conventional therapeutic modalities inevitably cause ablation of adjacent non-tumorous tissues, photodynamic therapy (PDT) offers a targeted cytotoxic strategy through a photosensitizing agent (PS). However, the hydrophobicity and lack of selective accumulation of promising PS compounds such as zinc(II) phthalocyanine (ZnPc) impedes their clinical translation as standalone agents. The present study sought to incorporate ZnPc within double-layer hollow mesoporous silica nanoparticles (DHMSN) as nanocarriers to enhance aqueous dispersibility and tumor specificity. Owing to their compartmentalized design, the hollow mesoporous silica nanoparticles (HMSN) demonstrated enhanced ultrasonic imaging contrast. Combined with the vaporization of the perfluorocarbon perfluoropentane (PFP), the HMSN-encapsulated ZnPc enabled real-time ultrasound monitoring of PDT treatment.In vivo, the innate thermal energy induced vaporization of the DHMSN-carried PFP to significantly amplify ultrasound signals from the tumor site. Results demonstrated biocompatibility, efficient PFP microbubble generation, and robust photocatalytic activity. Collectively, this investigation establishes ultrasound-guided PDT utilizing multi-layer HMSN as a targeted therapeutic strategy for cervical malignancies with mitigated toxicity.

Novel Organic-Inorganic Nanocomposite Hybrids Based on Bioactive Glass Nanoparticles and Their Enhanced Osteoinductive Properties.

Inorganic-organic hybrid biomaterials have been proposed for bone tissue repair, with improved mechanical flexibility compared with scaffolds fabricated from bioceramics. However, obtaining hybrids with osteoinductive properties equivalent to those of bioceramics is still a challenge. In this work, we present for the first time the synthesis of a class II hybrid modified with bioactive glass nanoparticles (nBGs) with osteoinductive properties. The nanocomposite hybrids were produced by incorporating nBGs in situ into a polytetrahydrofuran (PTHF) and silica (SiO2) hybrid synthesis mixture using a combined sol-gel and cationic polymerization method. nBGs ~80 nm in size were synthesized using the sol-gel technique. The structure, composition, morphology, and mechanical properties of the resulting materials were characterized using ATR-FTIR, 29Si MAS NMR, SEM-EDX, AFM, TGA, DSC, mechanical, and DMA testing. The in vitro bioactivity and degradability of the hybrids were assessed in simulated body fluid (SBF) and PBS, respectively. Cytocompatibility with mesenchymal stem cells was assessed using MTS and cell adhesion assays. Osteogenic differentiation was determined using the alkaline phosphatase activity (ALP), as well as the gene expression of Runx2 and Osterix markers. Hybrids loaded with 5, 10, and 15% of nBGs retained the mechanical flexibility of the PTHF-SiO2 matrix and improved its ability to promote the formation of bone-like apatite in SBF. The nBGs did not impair cell viability, increased the ALP activity, and upregulated the expression of Runx2 and Osterix. These results demonstrate that nBGs are an effective osteoinductive nanoadditive for the production of class II hybrid materials with enhanced properties for bone tissue regeneration.

Intelligent Biogenic Missile for Two-Photon Fluorescence Imaging-Guided Combined Photodynamic Therapy and Chemotherapy in Tumors.

Photodynamic therapy (PDT) is a significant noninvasive therapeutic modality, but it is often limited in its application due to the restricted tissue penetration depth caused by the wavelength limitations of the light source. Two-photon (TP) fluorescence techniques are capable of having an excitation wavelength in the NIR region by absorbing two NIR photons simultaneously, which offers the potential to achieve higher spatial resolution for deep tissue imaging. Thus, the adoption of TP fluorescence techniques affords several discernible benefits for photodynamic therapy. Organic TP dyes possess a high fluorescence quantum yield. However, the biocompatibility of organic TP dyes is poor, and the method of coating organic TP dyes with silica can effectively overcome the limitations. Herein, based on the TP silica nanoparticles, a functionalized intelligent biogenic missile TP-SiNPs-G4(TMPyP4)-dsDNA(DOX)-Aptamer (TGTDDA) was developed for effective TP bioimaging and synergistic targeted photodynamic therapy and chemotherapy in tumors. First, the Sgc8 aptamer was used to target the PTK7 receptor on the surface of tumor cells. Under two-photon light irradiation, the intelligent biogenic missile can be activated for TP fluorescence imaging to identify tumor cells and the photosensitizer assembled on the nanoparticle surface can be activated for photodynamic therapy. Additionally, this intelligent biogenic missile enables the controlled release of doxorubicin (DOX). The innovative strategy substantially enhances the targeted therapeutic effectiveness of cancer cells. The intelligent biogenic missile provides an effective method for the early detection and treatment of tumors, which has a good application prospect in the real-time high-sensitivity diagnosis and treatment of tumors.

Precursor carboxy-silica for functionalization with interactive ligands. IV. Carbodiimide assisted preparation of immobilized antibody stationary phases for high performance immuno-affinity chromatography of human serum.

In this Part IV of the article series dealing with the functionalization of the precursor carboxy silica with various chromatographic ligands, immuno affinity (IA) columns were prepared with immobilized anti-apolipoprotein B (AAP B) and anti-haptoglobin (AHP) antibodies for use in immuno affinity chromatography (IAC) in the aim of selectivily capturing their corresponding antigens from healthy and cancer human sera. Diseased human serum with adenocarcinoma cancer was selected as a typical diseased biological fluid. Besides preferentially capturing their corresponding antigens, the AAP B column captured from disease-free and cancer sera, 34 proteins and 33 proteins, respectively, while the AHP column enriched 38 and 47 proteins, respectively. This nonspecific binding can be attributed to the many proteins human serum have, which could mediate protein-protein interactions thus leading to the so-called "sponge effect". This kind of behavior can be exploited positively in the determination of differentially expressed proteins (DEPs) for diseased serum with respect to healthy serum and in turn allow the identification of an array of potential biomarkers for cancer. In fact, For AHP column, 13 upregulated and 22 downregulated proteins were identified whereas for AAP B column the numbers were 23 and 10, respectively. The DEPs identified with both columns match those reported in the literature for other types of cancers. The different expression of proteins in each IAC column can be related to the variability of protein-protein interactions. In addition, an array of a few biomarkers is more indicative of a certain disease than a single biomarker.

Overcoming the Blood-Brain Tumor Barrier with Docetaxel-Loaded Mesoporous Silica Nanoparticles for Treatment of Temozolomide-Resistant Glioblastoma.

While temozolomide (TMZ) has been a cornerstone in the treatment of newly diagnosed glioblastoma (GBM), a significant challenge has been the emergence of resistance to TMZ, which compromises its clinical benefits. Additionally, the nonspecificity of TMZ can lead to detrimental side effects. Although TMZ is capable of penetrating the blood-brain barrier (BBB), our research addresses the need for targeted therapy to circumvent resistance mechanisms and reduce off-target effects. This study introduces the use of PEGylated mesoporous silica nanoparticles (MSN) with octyl group modifications (C8-MSN) as a nanocarrier system for the delivery of docetaxel (DTX), providing a novel approach for treating TMZ-resistant GBM. Our findings reveal that C8-MSN is biocompatible in vitro, and DTX@C8-MSN shows no hemolytic activity at therapeutic concentrations, maintaining efficacy against GBM cells. Crucially, in vivo imaging demonstrates preferential accumulation of C8-MSN within the tumor region, suggesting enhanced permeability across the blood-brain tumor barrier (BBTB). When administered to orthotopic glioma mouse models, DTX@C8-MSN notably prolongs survival by over 50%, significantly reduces tumor volume, and decreases side effects compared to free DTX, indicating a targeted and effective approach to treatment. The apoptotic pathways activated by DTX@C8-MSN, evidenced by the increased levels of cleaved caspase-3 and PARP, point to a potent therapeutic mechanism. Collectively, the results advocate DTX@C8-MSN as a promising candidate for targeted therapy in TMZ-resistant GBM, optimizing drug delivery and bioavailability to overcome current therapeutic limitations.

Tumor-targeted gypenoside nanodrug delivery system with double protective layers.

OBJECTIVES: Gypenoside (Gyp) is easily degraded in the gastrointestinal tract, resulting in its low bioavailability. We aimed to develop a tumor-targeted Gyp nanodrug delivery system and to investigate its antitumor effect in vitro. MATERIALS AND METHODS: We used Gyp as the therapeutic drug molecule, mesoporous silica (MSN) and liposome (Lipo) as the drug carrier and protective layers, and aptamer SYL3C as the targeting element to establish a tumor-targeted nanodrug delivery system (i.e., SYL3C-Lipo@Gyp-MSN). The characteristics of SYL3C-Lipo@Gyp-MSN were investigated, and its drug release performance, cell uptake, and antitumor activity in vitro were evaluated. RESULTS: A tumor-targeted Gyp nanodrug delivery system was successfully prepared. The SYL3C-Lipo@Gyp-MSN was spherical or ellipsoidal; had good dispersion, which enabled it to specifically target and kill the liver tumor cell HepG2; and effectively protected the early leakage of Gyp. CONCLUSIONS: We have established a tumor-targeted nanodrug delivery system that can target and kill liver cancer cells and may provide a strategy for preparing new nanodrug-loaded preparations of traditional Chinese medicine.

Remarkable enhancement of cinnamaldehyde antimicrobial activity encapsulated in capped mesoporous nanoparticles: A new "nanokiller" approach in the era of antimicrobial resistance.

Combating antimicrobial resistance is one of the biggest health challenges because of the ineffectiveness of standard biocide treatments. This challenge could be approached using natural products, which have demonstrated powerful therapeutics against multidrug-resistant microbes. In the present work, a nanodevice consisting of mesoporous silica nanoparticles loaded with an essential oil component (cinnamaldehyde) and functionalized with the polypeptide ε-poly-l-lysine is developed and used as an antimicrobial agent. In the presence of the corresponding stimuli (i.e., exogenous proteolytic enzymes from bacteria or fungi), the polypeptide is hydrolyzed, and the cinnamaldehyde delivery is enhanced. The nanodevice's release mechanism and efficacy are evaluated in vitro against the pathogenic microorganisms Escherichia coli, Staphylococcus aureus, and Candida albicans. The results demonstrate that the new device increases the delivery of the cinnamaldehyde via a biocontrolled uncapping mechanism triggered by proteolytic enzymes. Moreover, the nanodevice notably improves the antimicrobial efficacy of cinnamaldehyde when compared to the free compound, ca. 52-fold for E. coli, ca. 60-fold for S. aureus, and ca. 7-fold for C. albicans. The enhancement of the antimicrobial activity of the essential oil component is attributed to the decrease of its volatility due to its encapsulation in the porous silica matrix and the increase of its local concentration when released due to the presence of microorganisms.

A composite hydrogel loaded with the processed pyritum promotes bone repair via stimulate the osteogenic differentiation of BMSCs.

Tissue engineering shows promise in repairing extensive bone defects. The promotion of proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) by biological scaffolds has a significant impact on bone regeneration outcomes. In this study we used an injectable hydrogel, known as aminated mesoporous silica gel composite hydrogel (MSNs-NH2@GelMA), loaded with a natural drug, processed pyritum (PP), to promote healing of bone defects. The mechanical properties of the composite hydrogel were significantly superior to those of the blank hydrogel. In vitro experiments revealed that the composite hydrogel stimulated the osteogenic differentiation of BMSCs, and significantly increased the expression of type I collagen (Col 1), runt-related transcription factor 2 (Runx 2), alkaline phosphatase (ALP), osteocalcin (OCN). In vivo experiments showed that the composite hydrogel promoted the generation of new bones. These findings provide evidence that the composite hydrogel pyritum-loaded holds promise as a biomaterial for bone repair.

Thermo-catalytic pyrolysis of sewage sludge and techno-economic analysis: The effect of synthetic zeolites and natural sourced catalysts.

This work focuses to the value added utilization of animal sewage sludge into gases, bio-oil and char using synthetic zeolite (ZSM-5 and Y-zeolite) and natural sourced (diatomite, kaolin, perlite) materials as catalysts. Pyrolysis was performed in a one-stage bench-scale reactor at temperatures of 400 and 600 °C. The catalyst was mixed with the raw material before the pyrolysis. Catalysts had a significant effect on the yield of products, because the amount of volatile products was higher in their presence, than without them. In case of kaolin, due to the structural transformation occurring between 500-600 °C, a significant increase in activity was observed in terms of pyrolysis reactions resulting in volatiles. The hydrogen content of the gas products increased significantly at a temperature of 600 °C and in thermo-catalysts pyrolysis. In the presence of catalysts, bio-oil had more favourable properties.