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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.
Subject(s)
Animals , Mice , Menthol/pharmacology , Actins/metabolism , Endothelial Cells/metabolism , Nanoparticles/chemistryABSTRACT
Objective@#The antibacterial properties and bonding strength of 3M orthodontic adhesive resin modified by chlorhexidine acetate (CHA) composite mesoporous silica were investigated.@*Methods@# CHA with different mass fractions was encapsulated in mesoporous silica nanoparticles (MSNs) (denoted CHA@MSNs). Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) were used to characterize the samples. The 3M Z350XT flow resin was divided into 4 groups: group A: 3M+CHA@MSNs (0%); group B: 3M+CHA@MSNs (3%); group C: 3M+CHA@MSNs (5%); and group D: 3M+CHA@MSNs (6.4%), with mass scores of 0%, 3%, 5%, and 6.4%, respectively. The shear strength of the modified adhesive was tested by a universal electronic material testing machine, the adhesive residue was observed by a 10 × magnifying glass, and the adhesive Remnant index (ARI) was calculated. The four groups of modified adhesives were cultured with Streptococcus mutans. The OD540 value of the bacterial solution was measured by a spectrophotometer, and the amount of plaque attachment was observed by scanning electron microscopy to evaluate the antibacterial performance of the adhesives.@*Results@#Infrared spectroscopic analysis of CHA@MSNs showed that CHA was successfully loaded onto MSNs. Under scanning electron microscopy, it could be seen that, after Cha was combined with MSNs, the structure of MSNs changed, as the boundary was fuzzy and aggregated into a layered structure. A comparison of shear strength revealed a statistically significant difference between the groups containing CHA@MSNs and the groups without CHA@MSNs (P<0.05). The value of the shear strength in group D decreased the most, while there was no statistically significant difference between group B and group C (P > 0.05). There was no statistical significance across all groups (P > 0.05), suggesting that the addition of CHA@MSNs had little effect on the bracket shedding. The OD540 value of bacterial fluid indicated that the difference among groups A, B and C was statistically significant (P < 0.05), and the antibacterial effect of group C was the best; there was no statistically significant difference between group C and group D (P > 0.05).@*Conclusions@#Therefore, adding 5% CHA@MSN antibacterial agent significantly improved the antibacterial effect and did not affect the bond strength.
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Objective @#To fabricate a co-delivery system of curcumin (CUR) and siRNA based on mesoporous silica nanoparticles (MSN) and investigate its potential application in inducing macrophage M2 polarization.@*Methods@# MSNs were synthesized using the conventional sol-gel method. The interior mesochannels were occupied by small-molecule CUR, while the exterior surface was adsorbed by cationic polymeric polyethyleneimine (PEI) to link the negatively charged siRNA molecules to formulate the (CUR@MSN)PEI/siRNA co-delivery system. The formulation process was monitored by transmission electron microscopy(TEM). The MTT assay was used to evaluate the cytotoxicity in RAW264.7 cells under various concentrations of nanoparticles. Confocal laser scanning microscopy and TEM were used to observe cell internalization using FAM-labeled siRNA. GAPDH-targeting siRNA was used to prepare nanoparticles and then was transfected into RAW264.7 cells to observe the silencing efficiency of target genes. The knockdown efficiency was examined by real-time quantitative PCR. The related control groups were untreated cells, CUR delivery only and the co-delivery of CUR and siRNA negative control. By loading miRNA-130a-3p antisense oligonucleotide (ASO) to transfect RAW264.7 cells, the effects on the polarization of macrophages were observed. The M2 polarization marker arginase 1 (Arg-1) was measured by western blotting. The related control groups were untreated cells, CUR delivery only and co-delivery of CUR and miRNA negative control. @* Results @# The (CUR@MSN)PEI/siRNA co-delivery system was successfully formulated. The nanoparticles exhibited dose-dependent cytotoxicity, and the cell viability was maintained over 90% when the nanoparticle concentration was less than 10 μg/mL. A high cell uptake efficiency was observed, and the target gene knockdown efficiency was greater than 80% (P < 0.05 vs. all the other groups). The CUR delivery-only group and co-delivery of the CUR-and miRNA-negative control group improved Arg-1 expression ~ 3-fold (P < 0.05 vs. untreated cells). Using the co-delivery of CUR and ASO, synergistic effects were obtained, and Arg-1 expression was increased ~ 8-fold (P < 0.05 vs. all the other groups).@*Conclusion @#The CUR-siRNA co-delivery system can effectively transfect macrophages and synergistically induce M2 polarization.
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Abstract Objective There is increasingly common the consumption more times a day of foods and acidic drinks in the diet of the population. The present study aimed to evaluate and compare the effects of a calcium mesoporous silica nanoparticle single application of other calcium and/or fluoride products in reducing the progression of dental erosion. Methodology Half of the eroded area was covered of 60 blocks of enamel, after which the block was submitted to the following treatments: (Ca2+-MSN), casein phosphopeptide-amorphous calcium phosphate (CPP-ACP); CPP-ACP/F-(900 ppm F−); titanium tetrafluoride (TiF4 1%) (positive control); sodium fluoride (NaF 1.36%) (positive control); and Milli-Q® water (negative control) before being submitted to a second erosive challenge. A surface analysis was performed via a three-dimensional (3D) noncontact optical profilometry to assess the volumetric roughness (Sa) and tooth structure loss (TSL) and and through scanning electron microscopy (MEV). An analysis of variance (ANOVA) and Tukey's test were performed. Results Regarding Sa, all experimental groups exhibited less roughness than the control (p<0.05). The TSL analysis revealed that the Ca2+-MSN and NaF groups were similar (p>0.05) and more effective in minimizing tooth loss compared with the other groups (p<0.05). Conclusions The Ca2+-MSN and NaF treatments were superior compared with the others and the negative control.
Subject(s)
Humans , Tooth Erosion , Tooth Remineralization , Nanoparticles , Sodium Fluoride , Caseins , Calcium , Silicon Dioxide , FluoridesABSTRACT
OBJECTIVE: To construct a biomimetic delivery system (U251/MSN-DOX), and assess its application of glioma targeted therapy. METHODS: U251 cell membrane was coated on the surface of mesoporous silica nanoparticles(MSN) by co-extrusion to prepare cell membrane biomimetic nanoparticles U251/MSN-DOX. The particle size, potential and morphology were characterized. The physical characteristics, loading content (LC) and encapsulation efficiency (EE) of these nanoparticles were determined. Their toxicity of normal cells was investigated. Their cellular uptake of different formulations in U251 was studied by flow cytometry and fluorescence confocal microscope. Additionally, we assessed the transmembrane transport efficiency of nanoparticles via in vitro BBB. RESULTS: The cell membrane-coated nanoparticles U251/MSN were spherical, and a distinct "core-shell" structure could be observed. The particle size was (135.70±3.85) nm, the LC was (18.57±2.17)%, and the EE was (64.99±2.52)%. The cell experiment showed that U251/MSN had low cytotoxicity and U251/MSN-DOX exhibited stronger cellular uptake ability and BBB transporting efficiency. CONCLUSION: The glioma cell membrane can be coated on the surface of MSN to construct biomimetic nanoparticles U251/MSN. The biomimetic nanoparticles not only are capable of targeting the homologous tumor cells, but also show the enhanced ability to penetrate BBB, which indicate potential applications in the field of tumor targeted drug delivery especially in brain tumor.
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Until now, great progress has been made in anti-tumor therapy. A series of novel anti-tumor drugs, such as molecular targeted drugs and monoclonal antibodies, have been emerging one after another, which have benefited a great number of tumor patients in different degrees. However, there are still many dilemmas in clinical anti-tumor therapy at present, for instance, obvious side effects, tumor resistance and so on. In recent years, the nano drug delivery system with mesoporous silica as the carrier has overcome many flaws of traditional anti-tumor treatment to a certain extent, especially the mesoporous silica nanosystem for controlling reactive oxygen species generation which has excellent tumor targeting property and biocompatibility, and minimal injury effects on normal tissue cells. So it has been regarded as one of the most promising agents in clinical application by playing significant anti-tumor roles through multiple approaches. This paper reviews this kind of potent nanosystem and its application to anti-tumor therapy.
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@#Objective: To construct indocyanine green-loaded silica nanoparticles (ICG@MSNs) and evaluate their killing effect on cervical cancer HeLa cells. Methods: Mesoporous silica nanoparticles (MSNs) were synthesized by template method, and indocyanine green (ICG) containing photothermal agent was loaded to prepare ICG@MSNs with photothermal effect, which were applied in the research of HeLa cells in vitro. Results: The particle of ICG@MSNs was uniform and in regular spherical shape with the size about 200 nm. ICG@MSNs was similar photothermal effect with pure ICG. Cell endocytosis experiments showed that ICG encapsulated in silica nanoparticles is more likely to be endocytosed by tumor cells, and then played a photothermal role in killing cervical cancer HeLa cells. On the other hand, cytotoxicity experiments showed that under the irradiation of 808 nm laser, ICG@MSNs significantly increased cytotoxicity, which could significantly kill cervical cancer HeLa cells. Conclusion: ICG@MSNs has good stability and biocompatibility, as well as good thermogenesis. It’s photothermal treatment effect on tumor is obvious, which has a good prospect for the treatment of cervical cancer.
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In recent years, mesoporous silica nanoparticles (MSNs) have been widely used in the construction of various intelligent drug delivery systems due to their unique and excellent properties. The stimuli-responsive drug delivery system based on mesoporous silica nanoparticles can effectively load anticancer drugs and target them to tumor cells, and then responsively release anticancer drugs under the action of specific stimulation signals. The method of specifically delivering anticancer drugs to target sites not only can greatly improvethe drug efficacy, but also effectively reduce the side effects of anticancer drugs on normal tissues and organs. Thereby the advantages of anticancer drugs in tumor therapy are improved. In this paper, the applications and developments of stimuliresponsive mesoporous silica nano drug delivery systems in tumor therapy were summarized.
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Mesoporous silica nanoparticles (MSNs) have been widely used as drug carriers in the diagnosis and treatment of diseases due to their specific characteristics, which include a large surface area, ordered mesoporous structures, easy surface modification and feasible sustained release action for encapsulated drugs. With the research development of MSNs, the biodegradability and removability of mesoporous silica nanomaterials have attracted considerable attention in the clinical application of the MSNs-based formulations. This paper was prepared to emphasize the preparation approaches of biodegradable mesoporous silica nanoparticles through the metal oxide doping method and the organic compound doping method. We discussed the biodegradable mechanism and process of such nanoparticles, and finally, provided an insightful and helpful review of the prospective application of the biodegradable mesoporous silica nanoparticles in medical field.
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Objective: To prepare a series of polyethylene (PEG)-modified mesoporous silica nanoparticles (MSNs-PEG) used for danshensu delivery carrier. Methods: By the co-hydrolysis method with silica coupling agent, the content of the azide groups was controlled into MSNs. The structures of MSNs-PEG were characterized by FTIR, XRD, and TEM analyses. The results showed that PEG chains have been grafted on the surface of MSNs. The safety of MSNs-PEG carrier was preliminarily evaluated by MTT, the release rule of MSNs-PEG was investigated by in vitro release experiment. Results: PEG can be effectively and controlled grafted onto MSNs. The MSNs-PEG have the good stability in aqueous solution. The loading rate of MSNs-PEG was higher in the experimental results of danshensu. The drug loading and entrapment efficiency were 6.8 % and 22.8 %. The graft of PEG could change the release of the drug, which could effectively prolong the time of drug release. And with the increase of the amount of PEG (mass fraction), the release time of danshensu could be prolonged effectively. Conclusion: The click chemistry method is easy to control the PEG graft content, and effectively controls the release rate of danshensu.
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Objective: To prepare polyacrylic acid grafted arsenic trioxide-loaded pH-responsive mesoporous silica nanoparticles (PAA-ATO-MSNs) and to investigate their physicochemical properties, in vitro release behavior, and pharmacokinetics in rats. Methods: PAA was covalently attached to the exterior surface of amino group functionalized MSNs prepared by co-condensation method and ATO was loaded into them by electrostatic adsorption. Transmission electron microscope (TEM), small angle X-ray diffraction (SAXRD), nitrogen adsorption, thermogravimetric analysis (TGA), fourier transform infrared (FT-IR) spectra, and laser particle size analyzer were used to determine the physicochemical properties. The entrapment efficiency (EE) and drug loading (DL) of PAA-ATO-MSNs were investigated with the method of high speed centrifugation combined with inductively coupled plasma emission spectrum (ICP). The drug release behavior of PAA-ATO-MSNs was studied using dynamic dialysis method, PBS (pH 5.0, 6.0, and 7.4) chosen as release media. Pharmacokinetic behavior of PAA-ATO-MSNs after iv injection in rats was studied. Results: Morphology of PAA-ATO-MSNs was spherical and the mean particle size, Zeta potential, EE, and DL of PAA-ATO-MSNs were (158.60 ± 1.32) nm, (-28.40 ± 0.34) mV, (40.95 ± 3.21)%, and (11.42 ± 1.75)%, respectively. In vitro release behavior of PAA-ATO-MSNs showed pH-responsive characteristic and the cumulative release amount was increased with the decrease of pH value. Compared with ATO-Sol and ATO-MSNs group, t1/2β was significantly prolonged and AUC was significantly increased (P < 0.01). Conclusion: Release of ATO from PAA-ATO-MSNs showed the obvious pH-responsive characteristic and sustained-release in vitro and PAA-ATO-MSNs could improve the pharmacokinetic behavior in rats. PAA-MSNs might be promising carrier to load ATO for cancer therapy.
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OBJECTIVE: To prepare and evaluate the novel core-shell structural phospholipid-functionalized mesoporous silica nanoparticles (MSN-LP) modified with angiopep-2 (ANG-MSN-LP). METHODS: Mesoporous silica nanoparticles (MSN) was synthesized by the modified Stober method. MSN-PTX was prepared by saturated solution adsorption method. ANG-MSN-LP was developed by selfassembly and film hydration method. By using dialysis bag method to investigate the in vitro drug release characteristics and MTT method to investigate the cytotoxicity on HBMEC and C6 cells. The transport ability and effects on cell cycle of the carrier was investigated by the BBB monolayer model. RESULTS: MSN was synthesized with high specific surface area (SBET, 425 m · g-1), cumulative pore volume (Vp, 0.37 cm · g-1) and pore size(3.5 nm). PTX was highly encapsulated (drug loading efficiency up to 11.1%) into MSN. Results of in vitro release showed that about 75.5% of PTX released from ANG-MSN-LP-PTX after 48 h and burst release was effectively reduced compared with MSN-PTX or PTX solution, indicating pronounced sustained-release characteristics. The good biocompatibility and low toxicity of ANG-MSN-LP were evaluated by HBMEC and C6 cells. The transport ratio was 2.49% for PTX, 2.72% for MSN-PTX, 4.45% for MSN-LP-PTX and 10.74% for ANG-MSN-LP-PTX respectively. In addition, ANG-MSN-LP-PTX showed a higher cell number of G2-M phase of 40.92 ± 6.20%. CONCLUSION: ANG-MSN-LP is a prospective targeting drug delivery system for therapy of brain glioma. Meanwhile, saturated solution adsorption method can increase the drug loading efficiency highly.
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@#Mesoporous silica nanoparticle as drug carrier has become the new research focus in the field of nano-drug delivery system in recent years. In this study, paclitaxel-loaded msesoporous silica nanoparticle(PTX@MSN)was manufactured by the solvent adsorption. In vitro studies revealed that PTX@MSN was well dispersed in aqueous medium with particle size of 250 nm, the potential of -(8. 01±1. 81)mV and drug loading efficiency of(23. 76±1. 14)%. PTX@MSN showed the sustained-release characteristics with the cumulative PTX of release(23. 62±2. 15)% at 24 h. In additions, the cytotoxicity investigation indicated that blank MSNs were biocompatible while PTX@MSN group showed improved in vitro anti-tumor activity against HepG2 cell when compared with Taxol group. In conclusion, MSN is a promising platform to build drug delivery systems for tumor therapy.