Mesoporous Silicon Nanoparticles Research Articles

A novel antibacterial and wear-resistant strategy based on metal surface micro-texture nitriding coupled functional mesoporous silicon coating

Modified metal layers coupling durable antifouling and antibacterial properties have garnered considerable interest in various fields, including but not limited to medical equipment, kitchen utensils, public facilities, and specific industrial applications, such as transportation, energy utilization, and aerospace. Nevertheless, wear and corrosion resulting from harsh operating environments can significantly compromise the modified metal layers, leading to diminished antifouling and antibacterial capabilities. Currently, maintaining excellent antibacterial properties on the surface of metal-modified layers under complex working conditions remains a key challenge for metal protection technology. Herein, we innovatively propose a ternary collaborative strategy to optimize and extend the antifouling and antibacterial activity of metal substrate surfaces. Firstly, laser surface texturing (LST) is used to create micro-textured topography on the metal surface to serve as a reservoir for collecting debris and storing functionalized nanoparticles. Then, the surface micro-textures are treated with plasma nitriding to form a wear-resistant passivation layer that protects the aforementioned microstructures. Finally, a lubricant containing functional mesoporous silicon nanoparticles (Ag2O-MSNs@OTES) is coated on the metal surface, which not only reduces the friction coefficient but also achieves antibacterial and antifouling effects by continuously releasing silver ions from the mesoporous silicon spheres. Employing the aforementioned ternary coordination strategy, the fabricated coupling layer exhibits not only exceptional antifriction and wear properties but also remarkable antibacterial efficacy against both E. coli and S. aureus, attributed to the Ag2O-MSNs@OTES. Therefore, the wear-resisting and antibacterial coupling layer for the protection of metal surfaces has promising and versatile applications in wide areas.

Theranostic Nanoplatform Based on Polydopamine-Coated Magnetic Mesoporous Silicon for Precise Cancer Triplex Nanotherapy and Multimodal Imaging.

Although targeted therapy has revolutionized oncotherapy, engineering a versatile oncotherapy nanoplatform integrating both diagnostics and therapeutics has always been an intractable challenge to overcome the limitations of monotherapy. Herein, a theranostics platform based on DI/MP-MB has successfully realized the fluorescence detection of disease marker miR-21 and the gene/photothermal/chemo triple synergetic cancer therapy, which can trace the tumor through photothermal and fluorescence dual-mode imaging and overcome the limitations of monotherapy to improve the treatment efficiency of tumors. DI/MP-MB was prepared by magnetic mesoporous silicon nanoparticles (M-MSNs) loaded with doxorubicin (Dox) and new indocyanine green (IR820), and subsequently coating polydopamine as a "gatekeeper", followed by the surface adsorbed with molecular beacons capable of targeting miR-21 for responsive imaging. Under the action of enhanced permeability retention and external magnetic field, DI/MP-MB were targeted and selectively accumulated in the tumor. MiR-21 MB hybridized with miR-21 to form a double strand, which led to the desorption of miR-21 MB from the polydopamine surface and the fluorescence recovery to realize gene silencing and fluorescence imaging for tracking the treatment process. Meanwhile, with the response to the near-infrared irradiation and the tumor's microacid environment, the outer layer polydopamine will decompose, releasing Dox and IR820 to realize chemotherapy and photothermal therapy. Finally, the ability of DI/MP-MB to efficiently suppress tumor growth was comprehensively assessed and validated both in vitro and in vivo. Noteworthily, the excellent anticancer efficiency by the synergistic effect of gene/photothermal/chemo triple therapy of DI/MP-MB makes it an ideal nanoplatform for tumor therapy and imaging.

Highly Efficient Separation of Ethanol Amines and Cyanides via Ionic Magnetic Mesoporous Nanomaterials.

Simple and efficient sample pretreatment methods are important for analysis and detection of chemical warfare agents (CWAs) in environmental and biological samples. Despite many commercial materials or reagents that have been already applied in sample preparation, such as SPE columns, few materials with specificity have been utilized for purification or enrichment. In this study, ionic magnetic mesoporous nanomaterials such as poly(4-VB)@M-MSNs (magnetic mesoporous silicon nanoparticles modified by 4-vinyl benzene sulfonic acid) and Co2+@M-MSNs (magnetic mesoporous silicon nanoparticles modified by cobalt ions) with high absorptivity for ethanol amines (EAs, nitrogen mustard degradation products) and cyanide were successfully synthesized. The special nanomaterials were obtained by modification of magnetic mesoporous particles prepared based on co-precipitation using -SO3H and Co2+. The materials were fully characterized in terms of their composition and structure. The results indicated that poly(4-VB)@M-MSNs or Co2+@M-MSNs had an unambiguous core-shell structure with a BET of 341.7 m2·g-1 and a saturation magnetization intensity of 60.66 emu·g-1 which indicated the good thermal stability. Poly(4-VB)@M-MSNs showed selective adsorption for EAs while the Co2+@M-MSNs were for cyanide, respectively. The adsorption capacity quickly reached the adsorption equilibrium within the 90 s. The saturated adsorption amounts were MDEA = 35.83 mg·g-1, EDEA = 35.00 mg·g-1, TEA = 17.90 mg·g-1 and CN-= 31.48 mg·g-1, respectively. Meanwhile, the adsorption capacities could be maintained at 50-70% after three adsorption-desorption cycles. The adsorption isotherms were confirmed as the Langmuir equation and the Freundlich equation, respectively, and the adsorption mechanism was determined by DFT calculation. The adsorbents were applied for enrichment of targets in actual samples, which showed great potential for the verification of chemical weapons and the destruction of toxic chemicals.

PH and temperature dual-responsive hollow mesoporous silica nanoparticles for drug encapsulation and delivery

In this work, pH and temperature dual-responsive drug delivery vehicles (CDs/PNVCL@HMSNs) with 57.05% drug loading efficiency were prepared. Hollow mesoporous silicon nanoparticles (HMSNs) were synthesized by selective etching. The mixed shells on the surface of HMSNs were composed of carbon dots (CDs) and poly (N-vinylcaprolactam) (PNVCL), which were linked to HMSNs via Schiff base reaction. At room environment (pH = 7.4, T = 25 °C), PNVCL was stretched, so that the model drug Doxorubicin (DOX) could be transported freely through the mesopores. In the blood stream (pH = 7.4, T = 37 °C), PNVCL was collapsed, and DOX was encapsulated to form PNVCL@HMSNs-DOX. CDs were grafted to give CDs/PNVCL@HMSNs-DOX and could further inhibit the leakage of drugs. At the acidic environment of the tumor site, Schiff base bonds broke, leading to shell shedding and DOX release. The drug release could be real-time monitored by the change in fluorescence intensity, which was confirmed by the linear fitting of the fluorescence strength of CDs and the percentage of DOX released. CDs/PNVCL@HMSNs are intriguing drug delivery systems (DDSs), which can combine real-time monitoring and control of drug release.

Hierarchical mesoporous silicon and albumin composite microparticles delivering DOX and FU for liver cancer treatment

Drug delivery systems based on hydrogel microcarriers have shown enormous achievements in tumor treatment. Current research direction mainly concentrated on the improvement of the structure and function of the microcarriers to effectively deliver drugs for enhanced cancer treatment with decreased general toxicity. Herein, we put forward novel hierarchical mesoporous silicon nanoparticles (MSNs) and bovine serum albumin (BSA) composite microparticles (MPMSNs@DOX/FU) delivering doxorubicin (DOX) and 5-fluorouracil (FU) for effective tumor therapy with good safety. The DOX and FU could be efficiently loaded in the MSNs, which were further encapsulated into methacrylate BSA (BSAMA) microparticles by applying a microfluidic technique. When transported to the tumor area, DOX and FU will be persistently released from the MPMSNs@DOX/FU and kept locally to lessen general toxicity. Based on these advantages, MPMSNs@DOX/FU could observably kill liver cancer cells in vitro, and evidently suppress the tumor development of liver cancer nude mice model in vivo. These results suggest that such hierarchical hydrogel microparticles are perfect candidates for liver cancer treatment, holding promising expectations for impactful cancer therapy.

Magnetic natural lipid nanoparticles for oral treatment of colorectal cancer through potentiated antitumor immunity and microbiota metabolite regulation

The therapeutic efficacy of oral nanotherapeutics against colorectal cancer (CRC) is restricted by inadequate drug accumulation, immunosuppressive microenvironment, and intestinal microbiota imbalance. To overcome these challenges, we elaborately constructed 6-gingerol (Gin)-loaded magnetic mesoporous silicon nanoparticles and functionalized their surface with mulberry leaf-extracted lipids (MLLs) and Pluronic F127 (P127). In vitro experiments revealed that P127 functionalization and alternating magnetic fields (AMFs) promoted internalization of the obtained P127-MLL@Gins by colorectal tumor cells and induced their apoptosis/ferroptosis through Gin/ferrous ion-induced oxidative stress and magneto-thermal effect. After oral administration, P127-MLL@Gins safely passed to the colorectal lumen, infiltrated the mucus barrier, and penetrated into the deep tumors under the influence of AMFs. Subsequently, the P127-MLL@Gin (+ AMF) treatment activated antitumor immunity and suppressed tumor growth. We also found that this therapeutic modality significantly increased the abundance of beneficial bacteria (e.g., Bacillus and unclassified-c-Bacilli), reduced the proportions of harmful bacteria (e.g., Bacteroides and Alloprevotella), and increased lipid oxidation metabolites. Strikingly, checkpoint blockers synergistically improved the therapeutic outcomes of P127-MLL@Gins (+ AMF) against orthotopic and distant colorectal tumors and significantly prolonged mouse life spans. Overall, this oral therapeutic platform is a promising modality for synergistic treatment of CRC.

Mesoporous Silicon Nanoparticles with Liver-Targeting and pH-Response-Release Function Are Used for Targeted Drug Delivery in Liver Cancer Treatment.

This article aims to develop an aspirin-loaded double-modified nano-delivery system for the treatment of hepatocellular carcinoma. In this paper, mesoporous silica nanoparticles (MSN) were prepared by the "one-pot two-phase layering method", and polydopamine (PDA) was formed by the self-polymerization of dopamine as a pH-sensitive coating. Gal-modified PDA-modified nanoparticles (Gal-PDA-MSN) were synthesized by linking galactosamine (Gal) with actively targeted galactosamine (Gal) to PDA-coated MSN by a Michael addition reaction. The size, particle size distribution, surface morphology, BET surface area, mesoporous size, and pore volume of the prepared nanoparticles were characterized, and their drug load and drug release behavior in vitro were investigated. Gal-PDA-MSN is pH sensitive and targeted. MSN@Asp is different from the release curves of PDA-MSN@Asp and Gal-PDA-MSN@Asp, the drug release of PDA-MSN@Asp and Gal-PDA-MSN@Asp accelerates with increasing acidity. In vitro experiments showed that the toxicity and inhibitory effects of the three nanodrugs on human liver cancer HepG2 cells were higher than those of free Asp. This drug delivery system facilitates controlled release and targeted therapy.

Targeted Delivery of Peptide Nucleic Acid by Biomimetic Nanoparticles Based on Extracellular Vesicle-coated Mesoporous Silica Nanoparticles.

Peptide nucleic acid (PNA) plays an important role in antimicrobial activity, but its cellular permeability is poor. To overcome this limitation, we constructed biomimetic nanoparticles by using extracellular vesicle (EV)-coated mesoporous silicon nanoparticles (MSNs) to deliver PNA to Staphylococcus aureus (S. aureus) and improve its antisense therapeutic effect. MSN was prepared by the sol-gel method, and EV was extracted by affinity resin chromatography. EV was coated on MSN by simple sonication (50 W, 3 min) to prepare biomimetic nanoparticles with PNA-loaded MSN as the core and EV isolated from S. aureus as the shell. The MSN prepared by the sol-gel method had a uniform particle size (100 nm) and well-defined pore size for loading PNA with good encapsulation efficiency (62.92%) and drug loading (7.74%). The concentration of EV extracted by affinity resin chromatography was about 1.74 mg/mL. EV could be well coated on MSN through simple ultrasonic treatment (50 W, 3 min), and the stability and blood compatibility of MSN@ EV were good. Internalization experiments showed that EV could selectively enhance the uptake of biomimetic nanoparticles by S. aureus. Preliminary in vitro antibacterial tests revealed that PNA@MSN@EV exhibited enhanced antibacterial activity against S. aureus and had stronger bactericidal activity than free PNA and PNA@MSN at equivalent PNA concentrations (8 μM). Biomimetic nanoparticles based on EV-coated MSN offer a new strategy to improve the efficacy of PNA for the treatment of bacterial infections, and the technology holds promise for extension to the delivery of antibiotics that are traditionally minimally effective or prone to resistance.

Stable "snow lantern-like" aggregates of silicon nanoparticles suitable as a drug delivery platform.

Nanomedicine is a growing field where development of novel organic and inorganic materials is essential to meet the complex requirements for drug delivery. This includes biocompatibility, suitability for surface modifications, biodegradability, and stability sufficient to carry a drug payload through various tissues for the desired timespan. Porous silicon nanoparticles (pSi NP) are shown to have several beneficial traits in drug delivery in addition to a porous structure to maximize drug loading. The conventional synthesis of pSi NP using electrochemical etching is costly, time-consuming and requires large quantities of highly toxic hydrofluoric acid (HF). As such this research attempted a novel method to address these limitations. Mesoporous silicon nanoparticles were prepared by centrifugal Chemical Vapor Deposition (cCVD) without the use of HF. This process generated aggregates consisting of multiple primary particles fused into each other, similar to snowballs fused together in a snow-lantern (snowball pyramid). Our results demonstrated that the cCVD Si particles were versatile in terms of surface chemistry, colloidal stability, degradability, minimization of acute in vitro toxicity, and modulation of drug release. Dynamic light scattering, scanning electron microscopy, and cryogenic nitrogen adsorption isotherm measurements confirmed the overall size (210 nm), morphology, and pore size (14-16 nm) of the prepared materials. Agglomeration in phosphate-buffered saline (PBS) was minimized by PEGylation by a two-step grafting procedure that employed a primary amine linker. Finally, the release rate of a model drug, hydrocortisone, was evaluated with both PEGylated and pristine particles. Conclusively, these snow-lantern cCVD Si particles do indeed appear suitable for drug delivery.

Enhancing antitumor immunity with stimulus-responsive mesoporous silicon in combination with chemotherapy and photothermal therapy.

Due to the immunosuppressive tumor microenvironment (TME) and potential systemic toxicity, chemotherapy often fails to elicit satisfactory anti-tumor responses, so how to activate anti-tumor immunity to improve the therapeutic efficacy remains a challenging problem. Photothermal therapy (PTT) serves as a promising approach to activate anti-tumor immunity by inducing the release of tumor neoantigens in situ. In this study, we designed tetrasulfide bonded mesoporous silicon nanoparticles (MSNs) loaded with the traditional drug doxorubicin (DOX) inside and modified their outer layer with polydopamine (DOX/MSN-4S@PDA) for comprehensive anti-tumor studies in vivo and in vitro. The MSN core contains GSH-sensitive tetrasulfide bonds that enhance DOX release while generating hydrogen sulfide (H2S) to improve the therapeutic efficacy of DOX. The polydopamine (PDA) coating confers acid sensitivity and mild photothermal properties upon exposure to near-infrared (NIR) light, while the addition of hyaluronic acid (HA) to the outermost layer enables targeted delivery to CD44-expressing tumor cells, thereby enhancing drug accumulation at the tumor site and reducing toxic side effects. Our studies demonstrate that DOX/MSN@PDA-HA can reverse the immunosuppressive tumor microenvironment in vivo, inducing potent immunogenic cell death (ICD) of tumor cells and improving anti-tumor efficacy. In addition, DOX/MSN@PDA-HA significantly suppresses tumor metastasis to the lung and liver. In summary, DOX/MSN@PDA-HA exhibits controlled drug release, excellent biocompatibility, and remarkable tumor inhibition capabilities through synergistic chemical/photothermal combined therapy.

Covalently hybridized carbon dots@mesoporous silica nanobeads as a robust and versatile phosphorescent probe for time-resolved biosensing and bioimaging.

Phosphorescence analyses have attracted broad attention due to their remarkable merits of the elimination of auto-fluorescence and scattering light. However, it remains a great challenge to develop novel materials with uniform size and morphology, stability, long lifetime, and aqueous-phase room temperature phosphorescence (RTP) characteristics. Herein, monodisperse and uniform RTP nanobeads were fabricated by an in situ covalent hybridization of carbon dots (CDs) and dendritic mesoporous silicon nanoparticles (DMSNs) via silane hydrolysis. The formation of Si-O-C and Si-C/N covalent bonds is beneficial for the fixation of vibrations and rotations of the luminescent centers. Specially, the nanopores of DMSNs provide a confined area that can isolate the triplet state of CDs from water and oxygen and thus ensure the occurrence of aqueous-phase RTP with an ultra-long lifetime of 1.195 s (seen by the naked eye up to 9 seconds). Through surface modifying folic acid (FA), CDs@DMSNs can serve as a probe to distinguish different cell lines that feature varying FA receptor expression levels. In addition, taking MCF-7 as the model, highly sensitive and quantitative detection (linear range: 103-106 cells per mL) has been achieved via an RTP probe. Furthermore, their potential applications in cellular and in vivo time-gated phosphorescence imaging have been proposed and demonstrated, respectively. This work would provide a new route to design CD-based RTP composites and promote their further applications in the medical and biological fields.

Harnessing the Materials Chemistry of Mesoporous Silicon Nanoparticles to Prepare “Armor-Clad” Enzymes

Harnessing the Materials Chemistry of Mesoporous Silicon Nanoparticles to Prepare “Armor-Clad” Enzymes

Biomimetic Inorganic Nanovectors as Tumor-Targeting Theranostic Platform against Triple-Negative Breast Cancer.

Mesoporous silicon nanoparticles (PSi NPs) are promising platforms of nanomedicine because of their good compatibility, high payload capacities of anticancer drugs, and easy chemical modification. Here, PSi surfaces were functionalized with bisphosphonates (BP) for radiolabeling, loaded with doxorubicin (DOX) for chemotherapy, and the NPs were coated with cancer cell membrane (CCm) for homotypic cancer targeting. To enhance the CCm coating, the NP surfaces were covered with polyethylene glycol prior to the CCm coating. The effects of the BP amount and pH conditions on the radiolabeling efficacy were studied. The maximum BP was (2.27 wt%) on the PSi surfaces, and higher radiochemical yields were obtained for 99mTc (97% ± 2%) and 68Ga (94.6% ± 0.2%) under optimized pH conditions (pH = 5). The biomimetic NPs exhibited a good radiochemical and colloidal stability in phosphate-buffered saline and cell medium. In vitro studies demonstrated that the biomimetic NPs exhibited an enhanced cellular uptake and increased delivery of DOX to cancer cells, resulting in better chemotherapy than free DOX or pure NPs. Altogether, these findings indicate the potential of the developed platform for cancer treatment and diagnosis.

Preparation of Mesoporous Si Nanoparticles by Magnesiothermic Reduction for the Enhanced Reactivity.

In this study, mesoporous silicon nanoparticles (M-Si) were successfully prepared by a magnesiothermic reduction of mesoporous silica nanoparticles, which were synthesized by a templated sol-gel method and used as the precursors. M-Si exhibited a uniform size distribution with an average diameter of about 160 nm. The measured BET surface area was 93.0 m2 g-1, and the average pore size calculated by the BJH method was 16 nm. The large internal surface area provides rich reaction sites, resulting in unique interfacial properties and reduced mass diffusion limitations. The mechanism of the magnesiothermic reduction process was discussed. The reactivity of prepared M-Si was compared with that of commercially available non-porous Si nanopowder (with the average diameter of about 30 nm) by performing simultaneous thermogravimetry and differential scanning calorimetry in the air. The results showed that the reaction onset temperature indicated by weight gain was advanced from 772 °C to 468 °C, indicating the promising potential of M-Si as fuel for metastable intermolecular composites.

Dual-responsive and controlled-release paclitaxel-loaded mesoporous silicon nanoparticles with cell membrane coating for homologous targeted therapy of tongue squamous cell carcinoma

The application of paclitaxel (PTX) for chemotherapy of tongue squamous cell carcinoma shows unavoidable damage to normal tissue, thus need to develop drug delivery and tumor-targeting nanomaterials. Mesoporous silica nanoparticles (MSNs) exhibit advantages including a convenient synthesis process, adjustable structure, high drug loading efficiency and low cytotoxicity. In this study, we synthesized PTX-loaded calcium carbonate-coated degradable disulfide-doped MSNs to construct a pH/redox dual-responsive controlled-release nanosystem. A high PTX loading rate of 9.68 ± 0.21% was measured with significantly accelerated release at low pH and in the presence of GSH. Moreover, surface decoration of the cell membrane was conducted to realize homologous targeted killing of tongue squamous cell carcinoma cells (PTX/ssMSN@CaCO3@TC), as confirmed by dynamic light scattering and gel electrophoresis analyses. Our nanocomposite material could be effectively taken up by Tca8113 cells but not by L929 and HeLa cells. Moreover, excellent tumor killing performance was measured both in vitro and in vivo. A total of 94.00 ± 1.66% and 98.12 ± 0.28% of Tca8113 cells were killed after culturing for 1 day and 3 days, respectively. This study developed a novel nanomaterial with the abilities of homologous targeting and dual-responsive release of PTX in tumor cells, exhibiting great value for the design of nanotargeting tumor killing drugs.

Antibacterial Effect of Acoustic Cavitation Promoted by Mesoporous Silicon Nanoparticles.

As-prepared mesoporous silicon nanoparticles, which were synthesized by electrochemical etching of crystalline silicon wafers followed by high-energy milling in water, were explored as a sonosensitizer in aqueous media under irradiation with low-intensity ultrasound at 0.88 MHz. Due to the mixed oxide-hydride coating of the nanoparticles' surfaces, they showed both acceptable colloidal stability and sonosensitization of the acoustic cavitation. The latter was directly measured and quantified as a cavitation energy index, i.e., time integral of the magnitude of ultrasound subharmonics. The index turned out to be several times greater for nanoparticle suspensions as compared to pure water, and it depended nonmonotonically on nanoparticle concentration. In vitro tests with Lactobacillus casei revealed a dramatic drop of the bacterial viability and damage of the cells after ultrasonic irradiation with intensity of about 1 W/cm2 in the presence of nanoparticles, which themselves are almost non-toxic at the studied concentrations of about 1 mg/mL. The experimental results prove that nanoparticle-sensitized cavitation bubbles nearby bacteria can cause bacterial lysis and death. The sonosensitizing properties of freshly prepared mesoporous silicon nanoparticles are beneficial for their application in mild antibacterial therapy and treatment of liquid media.

Effect of nanoparticles of different stiffness combined with menthol/curcumol on mechanical properties of bEnd.3 cells

This study aimed to investigate the effects of nanoparticles PLGA-NPs and mesoporous silicon nanoparticles(MSNs) of different stiffness before and after combination with menthol or curcumol on the mechanical properties of bEnd.3 cells. The particle size distributions of PLGA-NPs and MSNs were measured by Malvern particle size analyzer, and the stiffness of the two nanoparticles was quantified by atomic force microscopy(AFM). The bEnd.3 cells were cultured in vitro, and the cell surface morphology, roughness, and Young's modulus were examined to characterize the roughness and stiffness of the cell surface. The changes in the mechanical properties of the cells were observed by AFM, and the structure and expression of cytoskeletal F-actin were observed by a laser-scanning confocal microscope. The results showed that both nanoparticles had good dispersion. The particle size of PLGA-NPs was(98.77±2.04) nm, the PDI was(0.140±0.030), and Young's modulus value was(104.717±8.475) MPa. The particle size of MSNs was(97.47±3.92) nm, the PDI was(0.380±0.016), and Young's modulus value was(306.019±8.822) MPa. The stiffness of PLGA-NPs was significantly lower than that of MSNs. After bEnd.3 cells were treated by PLGA-NPs and MSNs separately, the cells showed fine pores on the cell surface, increased roughness, decreased Young's modulus, blurred and broken F-actin bands, and reduced mean gray value. Compared with PLGA-NPs alone, PLGA-NPs combined with menthol or curcumol could allow deepened and densely distributed surface pores of bEnd.3 cells, increase roughness, reduce Young's modulus, aggravate F-actin band breakage, and diminish mean gray value. Compared with MSNs alone, MSNs combined with menthol could allow deepened and densely distributed surface pores of bEnd.3 cells, increase roughness, reduce Young's modulus, aggravate F-actin band breakage, and diminish mean gray value, while no significant difference was observed in combination with curcumol. Therefore, it is inferred that the aromatic components can increase the intracellular uptake and transport of nanoparticles by altering the biomechanical properties of bEnd.3 cells.

Effects of Macrophage Polarization Induced by Mesoporous Silicon-Based Curcumin-siRNA Nanoparticles on the Proliferation of Tendon Stem Cells

Studies have shown that curcumin (CUR)-siRNA can improve excessive fibrosis in the repair of patellar tendon (PT) injury. First, mesoporous silicon nanoparticles (NPs) (MES-SiN) were prepared by a sol–gel method. The small molecule CUR was adsorbed in the internal pore canal of MES-Sin, and the cationic high molecular polyethyleneimine (PP) was adsorbed on the outer layer, which combined with negatively charged siRNA to form CUR@MES-SiN-PP/siRNA NPs. The preparation of NPs was observed by transmission electron microscopy (TEM). RAW264.7 macrophages were treated with different concentrations of NPs, and cell viability was determined by methyl tetrazolium (MTT) assay. The NPs were prepared by siRNA labeled with the fluorescent dye 6-carboxyfluorescein (FAM) and transfected into cells. The cellular uptake of the NPs was observed by confocal laser scanning microscopy (CLSM) and TEM. A total of 80 SPF SD rats (10 weeks of age) were randomly assigned into two groups to establish a PT injury model. The rats in experimental (Exp) group were injected with CUR@MES-SiN-PP/siRNA NP solution (2 μg/g) in the abdomen for 14 d, and those in control (Ctrl) group were injected with an equal dose of 1% dimethyl sulfoxide (DMSO). The rectus femoris of 24 rats were taken from each group 12 h and 1 d, 3 d, 5 d, 7 d, and 14 d after injury. Masson and hematoxylineosin were used to observe the degree of fibrosis of the PT tissue. The differentiation of macrophages was observed by flow cytometry, and the proliferation of tendon stem cells was observed by immunofluorescence approaches such as Pax7. The results suggested that CUR@MES-SiN-PP/siRNA NPs were successfully fabricated. The NPs showed dose-dependent cytotoxicity, the cell viability remained above 90% at concentrations below 10 μg/mL, and the NPs were ingested by higher cells. After injury, the fibrotic area of Exp group was drastically decreased (P <0.05), and the regenerated muscle fiber area was increased (P <0.05). The number of M2-type macrophages increased markedly 3 d, 5 d, 7 d, and 14 d after injury (P <0.05). Immunofluorescence showed that the proliferation of fluorescent cells 3 d after surgery was superior to that of Ctrl group (P <0.05).

PH-labile artificial natural killer cells for overcoming tumor drug resistance.

Natural killer (NK) cells exert cytotoxic effects against infected or stressed cells, such as tumor cells, without the limitation of major histocompatibility complex (MHC) I. NK cells secrete perforins to form tunnels to mediate the entry of granzyme into target cells. This strategy, selected by natural evolution, provides a feasible method for the delivery of antitumor drugs against intracellular targets, and avoids drug-resistant mechanisms in tumor cells, such as the pumping out of drugs mediated by multidrug resistance. We constructed pH-labile artificial NK cells (ANKC) based on nature to mediate high levels of drugs in tumor cells to overcome tumor drug resistance. Mesoporous silicon nanoparticles (MSNs) modified with benzaldehyde were designed to function as scaffolds for ANKC. Doxorubicin (Dox), a model antitumor drug, was loaded into the pores of MSNs. Melittin, a pore-forming peptide, was utilized as the gate for mesopores with an acid-labile Schiff base linkage. pH-labile ANKC released melittin and Dox in slightly acidic tumor microenvironments. Melittin, like perforin, assembled tunnels on the plasma membrane or endosome, ensuring the intracellular transportation of Dox. Dox, similar to granzyme, induced the apoptosis of tumor cells. The combinational treatment partially eased the drug resistance mechanism, such as pumping out of drugs, by continuous intracellular drug accumulation mediated by melittin pores. The pH-labile ANKC demonstrated significant Dox enrichment in drug-resistant MCF-7/Adr cells and MCF-7/Adr-based xenograft tumors in a mouse model, which eventually contributed to efficient inhibition of the proliferation and growth of MCF-7/Adr tumors. PH-labile ANKC provided a potential strategy to treat drug-resistant tumors.

The protective effect of puerarin-loaded mesoporous silicon nanoparticles on alcoholic hepatitis through mTOR-mediated autophagy pathway.

Puerarin, a bioactive flavone compound isolated from Pueraria (Wild.), provides hepatoprotection by anti-inflammatory, anti-alcoholism, and regulating mechanistic target of rapamycin (mTOR). Building evidence suggests that the activation of mTOR reduces liver injuries associated with alcohol consumption and metabolism. However, the poor water solubility, low bioavailability, and short half-life of puerarin hinder its clinical application. The utility of mesoporous silicon nanoparticles (MSNs) can improve traditional Chinese medicine limitations. Stober methods were used to fabricate MSNs@Pue, and the size, zeta potentials and drug encapsulation efficiency were characterized by a series of analytical methods. IVIS Imaging System demonstrated liver-targeted bio-distribution, and then high-throughput sequencing, immunoproteomics and ultrastructure methods indicated autophagy related protective mechanism, followed by curative effect evaluation for the treatment efficacy. An acute-on chronic ethanol-drinking according to Gao-binge model induced alcoholic hepatitis (AH) pathology and resulted in hepatic hyper-autophagy, which was improved with MSNs@Pue administration (puerarin: 30mM, 42mg/kg; intravenously [i.v.]). Ethanol-fed mice were found to have increased expression of autophagy-related proteins (Atg3, Atg7, LC3 and p62). In contrast, MSNs@Pue administration significantly decreased the expression of these proteins and alleviated fatty droplets infiltration in damaged liver. Furthermore, acute-on-chronic ethanol feeding also resulted in the activiation of ERK activation and mTOR expression, which were reversed with MSNs@Pue administration and better than the usage of puerarin alone. Results point to MSNs@Pue mediated ERK/mTOR signaling pathway activation as a possible protective strategy to improve AH, which provides a strategy and evidence for treating liver disease using an MSN delivery system.