介孔SiO_2纳米微球的生物相容性研究进展

介孔SiO2纳米微球(MSNs)具有良好的理化性能,在疾病诊治方面具有广阔的应用前景,但若要成功应用于人体,需要完善其生物相容性研究。MSNs对于细胞的毒性与MSNs能否被摄取进入细胞,以及进入细胞的量有关,并取决于细胞的类型和MSNs本身的性状。通过一系列物理和化学方法的改进,可以明显改善MSNs的血液相容性,降低溶血作用。介孔SiO2纳米微球经静脉注射后分布于动物的肝脏、脾脏、肾脏、心脏、肠胃、肌肉和肺脏,其毒性作用与浓度有关;MSNs作为一种异物进入体内后可能会诱发机体产生一定程度的超敏反应。介孔SiO2纳米微球具有较好的生物相容性,但其采用何种方式应用仍需进一步研究。     

季铵盐接枝聚膦腈微球的制备及抗菌活性

细菌感染引起的疾病问题在世界范围内引起广泛的关注。抗生素虽然能有效治疗细菌感染,但是不合理的使用及滥用会导致细菌产生耐药性。因此,解决细菌耐药性问题并研发出安全高效的非抗生素抗菌剂显得尤为迫切。通过在生物可降解型环交联型聚(环三膦腈-共-聚乙烯亚胺)微球(PHP)表面上接枝环氧丙基十二烷基二甲基氯化铵(DDEAC),成功制备了环交联型聚(环三膦腈-共-聚乙烯亚胺)接枝季铵盐微球(PHPD)。采用FTIR、XPS、TG、TEM和FESEM对微球的结构与形貌进行了表征分析,并研究了其抗菌活性和细胞毒性。实验结果表明,改性抗菌微球PHPD(50 μg/mL)对大肠杆菌(E.coli)和金黄色葡萄球菌(S.aureus)的抗菌率均达97.3%。复合材料克服了单独使用季铵盐DDEAC材料的高毒性缺陷,并且在实现高效抗菌的同时也具有很好的细胞相容性。因此,本研究对于开发安全高效的纳米抗菌剂具有一定的指导意义。      

用作关节腔滑膜切除的放射性镝锂硼玻璃微球的性能研究

制备了能用于切除关节腔滑膜的放射性硼酸镝锂(DyLB)玻璃微球,通过体外试验和动物试验研究了DyLB玻璃微球的降解性和生物相容性.实验结果表明:DyLB微球在SBF9模拟体液中发生非均匀性溶解,浸泡7d后,Dy3+的溶出量低于原始玻璃组成中Dy元素总量的0.0026wt%,Li+的溶出量则超过Li元素总量的53wt%.失重实验表明,DyLB微球具有部分生物可降解性,对所研究的三个组成,在SBF9中浸泡1d后,DyLB玻璃微球的总失重量约16%～43%;浸泡7d后,微球与SBF9模拟液反应达到平衡,失重量达到25%～55%.同时,DyLB微球具有良好的生物相容性,微球植入小鼠体内2周后,形貌发生变化并逐渐降解,期间没有引起组织损伤或异常炎症反应;DyLB微球经中子激活,活化后核纯度指标大于99.9%,符合临床应用要求.     

超临界流体技术制备吗啡/聚乳酸-聚乙二醇共聚物缓释微球

以L-聚乳酸-聚乙二醇三嵌段共聚物(PLLA-PEG-PLLA)为载体材料,通过超临界流体强制溶液分散技术制备吗啡/聚乳酸-聚乙二醇共聚物(MF/PLLA-PEG-PLLA)的复合微球,考察了PEG分子量的变化对微球性能的影响。通过表面形貌,粒径及粒径分布,载药量,包封率及释放性能来表征复合微球的各项性能;利用气相色谱法测定二氯甲烷和甲醇的残留量;通过溶血实验来评价复合微球的血液相容性。实验表明,所制备的复合微球呈球形或类球形形貌,平均粒径在1.99～6.20μm之间,载药量达到17.92%,包封率最高可至69.57%,复合微球的药物释放呈先突释后缓释的释药模式;二氯甲烷和甲醇的残留量分别为0.0076%和0.0016%;微球溶血率<1%,远小于国家标准5%,证明复合微球具有较好的血液相容性。     

悬浮聚合法制备功能型甲基丙烯酸酯类聚合物的研究与应用

甲基丙烯酸酯类微球具有与生物样品相容性好、易于修饰、无毒副作用等特点,在生物生化领域中具有重要作用。悬浮聚合法步骤简单、产物处理方便,是最常用的聚合物制备方法。以微球粒径及孔结构为指标,系统综述了悬浮聚合法制备甲基丙烯酸酯类聚合物的各个影响因素,并总结了此类填料在酶的固定化、分子印迹聚合物的制备、药物载体及金属离子吸附等方面的应用,最后对甲基丙烯酸酯类微球的发展趋势进行了展望。     

诺氟沙星明胶磁性微球的研制及表征

利用明胶的生物相容性及经戊二醛处理可使其固化的特性, 以Fe₃O₄作为磁性内核, 以液体石蜡为有机分散介质, 通过反相悬液冷冻凝聚法制备了强磁性的诺氟沙星明胶核壳微球, 用IR、SEM、TEM、UV/Vis等技术对微球进行了性能表征, 结果表明: 微球成球性好, 无粘连, 平均直径为5～10μm, Fe₃O₄的含量为19%, 明胶的含量为74.8%, 微球载药率(w/w)为6.2%, 药物包裹率为61.4%, 5h释放药物为74.4%, 微球具有较好的缓释性.     

生物可降解Mg-2Zn-0.2Mn合金的体外生物相容性

采用真空铸造技术制备了Mg-2Zn-0.2Mn三元镁合金,并对该合金体外生物生物相容性能进行了研究。采用血小板粘附、溶血率评价镁合金的血液相容性,采用细胞增殖实验(CCK-8)、细胞凋亡实验(AO/PI)评价镁合金的细胞相容性。结果表明:血小板粘附实验表明,与常用的AZ31B镁合金和316L不锈钢样品相比较,Mg-2Zn0.2Mn镁合金表面粘附的血小板数量少,且激活和团聚较轻微;溶血实验的结果表明Mg-2Zn0.2Mn的溶血率为4.7%,远小于AZ31B的80.9%溶血率。血小板黏附和溶血实验说明Mg-2Zn0.2Mn镁合金具有优异的血液相容性。细胞增殖和凋亡实验结果也表明,较AZ31B样品,Mg-2Zn0.2Mn样品表面显示了更好的内皮细胞粘附和增殖能力,说明Mg-2Zn0.2Mn镁合金具有很好的血液相容性和内皮细胞相容性,有望作为今后可降解血管支架的候选材料。     

PU/ST/SA复合微球的制备及血液相容性研究

采用预聚—扩链—中和—分散法合成PU水溶液,将PU、ST、SA溶液按质量比1∶1∶1、1∶1∶2、1∶1∶3进行复合,通过凝聚相分离法制备复合微球。由红外光谱分析样品的化学结构,发现PU与ST和SA之间通过氢键作用复合;由SEM观测微球表面及剖面的形态结构,发现复合微球平均粒径约为2~3mm,表面光滑且内部有很多均匀致密的管状孔隙,适合用作药物释放载体材料;血液相容性测试结果表明,复合微球的动态凝血时间、溶血率以及血小板消耗率均达到了与血液接触材料的国家标准,说明PU/ST/SA复合微球具有良好的血液相容性。     

荔枝状CaCO3@HA/Fe3O4磁性介孔多级微球的制备

为了克服常规的生物陶瓷微球缺乏靶向功能的缺点, 本研究制备了内核为CaCO₃, 外壳为磁性可调控羟基磷灰石(HA)的新型荔枝状多孔微球。结果表明: 抗肿瘤药物阿霉素(DOX)能有效地负载于磁性HA微球上, 并具备磁性靶向功能。此外, HA外壳具有良好的生物相容性和pH响应特性, 可在模拟酸性肿瘤细胞环境中控制DOX的释放, 有效杀死肿瘤细胞, 并在模拟正常细胞培养环境中减少对正常细胞的毒副作用。这种新型的微球材料具有超顺磁性能, 且微结构可控, 是一种智能化药物控释微球载体, 可以灵敏地释放DOX, 从而有效地实现抗肿瘤活性。     

静电喷雾法一步制备自显影Fe3O4@壳聚糖载药栓塞微球

采用静电喷雾法一步制备包裹着Fe₃O₄纳米粒子的壳聚糖复合微球(Fe₃O₄@CS微球),实现Fe₃O₄纳米粒子与微球同时合成。还可以按需制备粒径范围为90～1 000μm的Fe₃O₄@CS微球,以满足不同部位血管的临床栓塞要求。SEM显示微球形貌均匀且粒径分布均一((94±3)μm),体外降解实验证明了微球具有生物可降解性,磁共振成像测试表明所制备的Fe₃O₄@CS微球具有良好的临床成像能力,血液、细胞相容性评估证实Fe₃O₄@CS微球具有良好的生物相容性。负载盐酸阿霉素(DOX)的载药微球显示出典型的药物缓释曲线,72 h内DOX的累计释放率为28.82%。结果表明,这一步可控制备的自显影栓塞剂在经导管动脉栓塞术(TACE)未来应用中展示了巨大的潜力。     

In Situ Fabrication of Ultrasmall Gold Nanoparticles/2D MOFs Hybrid as Nanozyme for Antibacterial Therapy

As one of the common reactive oxygen species, H₂O₂ has been widely used for combating pathogenic bacterial infections. However, the high dosage of H₂O₂ can induce undesired damages to normal tissues and delay wound healing. In this regard, peroxidase‐like nanomaterials serve as promising nanozymes, thanks to their positive promotion toward the antibacterial performance of H₂O₂, while avoiding the toxicity caused by the high concentrations of H₂O₂. In this work, ultrasmall Au nanoparticles (UsAuNPs) are grown on ultrathin 2D metal–organic frameworks (MOFs) via in situ reduction. The formed UsAuNPs/MOFs hybrid features both the advantages of UsAuNPs and ultrathin 2D MOFs, displaying a remarkable peroxidase‐like activity toward H₂O₂ decomposition into toxic hydroxyl radicals (·OH). Results show that the as‐prepared UsAuNPs/MOFs nanozyme exhibits excellent antibacterial properties against both Gram‐negative (Escherichia coli) and Gram‐positive (Staphylococcus aureus) bacteria with the assistance of a low dosage of H₂O₂. Animal experiments indicate that this hybrid material can effectively facilitate wound healing with good biocompatibility. This study reveals the promising potential of a hybrid nanozyme for antibacterial therapy and holds great promise for future clinical applications.     

Enhanced antibacterial activity and mechanism studies of Ag/Bi2O3 nanocomposites

In this work, sphere-like Ag/Bi₂O₃ nanocomposites with the average size of ca. 170?nm were successfully synthesized by simple deposition-precipitation method. The antibacterial activities of as-prepared Ag/Bi₂O₃ nanocomposites were evaluated by minimal inhibitory concentration (MIC), minimal bactericidal concentration (MBC) and colony counting methods. It was found that Ag/Bi₂O₃ nanocomposites displayed greatly improved antibacterial ability against common pathogenic Gram-positive and Gram-negative bacteria in comparison with single-component Bi₂O₃ nanospheres. More importantly, Ag/Bi₂O₃ nanocomposites exhibited remarkably outstanding antibacterial activities against clinical drug-resistant bacteria. The antibacterial activity of Ag/Bi₂O₃ nanocomposite increased with the increase of Ag content and 15?wt% Ag/Bi₂O₃ nanocomposites showed the highest antibacterial activity. Furthermore, a plausible antibacterial mechanism of Ag/Bi₂O₃ nanocomposite was proposed. It was believed that the enhanced generation of H₂O₂ could lead to the membrane leakage of cytosol and the inactivation of respiratory chain dehydrogenaes, which was possibly responsible for the enhanced antibacterial activities of nanocomposites.     

Electrodeposition for antibacterial nickel-oxide-based coatings

Nickel-oxide-based films exhibiting antibacterial activity against both Gram-negative (Escherichia coli) and Gram-positive bacteria (Bacillus atrophaeus) have been fabricated by electrodeposition from aqueous solutions. However, after annealing of the films, no antibacterial activity has been observed. As-deposited films were found to consist of a mixture of nickel-oxide hydroxide and nickel hydroxide, while annealing resulted in the conversion of the films into pure NiO. Also, annealed films exhibited no production of H₂O₂, unlike as-deposited films. Thus, antibacterial activity of as-deposited films is related to the presence of nickel-oxide hydroxide/nickel hydroxide which results in the production of reactive oxygen species and antibacterial activity.     

All-in-One: Multifunctional Hydrogel Accelerates Oxidative Diabetic Wound Healing through Timed-Release of Exosome and Fibroblast Growth Factor

The treatment of diabetic wounds remains a major challenge in clinical practice, with chronic wounds characterized by multiple drug-resistant bacterial infections, angiopathy, and oxidative damage to the microenvironment. Herein, a novel in situ injectable HA@MnO₂/FGF-2/Exos hydrogel is introduced for improving diabetic wound healing. Through a simple local injection, this hydrogel is able to form a protective barrier covering the wound, providing rapid hemostasis and long-term antibacterial protection. The MnO₂/ε-PL nanosheet is able to catalyze the excess H₂O₂ produced in the wound, converting it to O₂, thus not only eliminating the harmful effects of H₂O₂ but also providing O₂ for wound healing. Moreover, the release of M2-derived Exosomes (M2 Exos) and FGF-2 growth factor stimulates angiogenesis and epithelization, respectively. These in vivo and in vitro results demonstrate accelerated healing of diabetic wounds with the use of the HA@MnO₂/FGF-2/Exos hydrogel, presenting a viable strategy for chronic diabetic wound repair.     

Evaluation of antibacterial property of hydroxyapatite and zirconium oxide‐modificated magnetic nanoparticles against Staphylococcus aureus and Escherichia coli

In the first section of this research, superparamagnetic nanoparticles (NPs) (Fe₃ O₄) modified with hydroxyapatite (HAP) and zirconium oxide (ZrO₂) and thereby Fe₃ O₄ /HAP and Fe₃ O₄ /ZrO₂ NPs were synthesised through co‐precipitation method. Then Fe₃ O₄ /HAP and Fe₃ O₄ /ZrO₂ NPs characterised with various techniques such as X‐ray photoelectron spectroscopy, X‐ray diffraction, scanning electron microscopy, energy dispersive X‐ray analysis, Brunauer–Emmett–Teller, Fourier transform infrared, and vibrating sample magnetometer. Observed results confirmed the successful synthesis of desired NPs. In the second section, the antibacterial activity of synthesised magnetic NPs (MNPs) was investigated. This investigation performed with multiple microbial cultivations on the two bacteria; Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). Obtained results proved that although both MNPs have good antibacterial properties, however, Fe₃ O₄ /HAP NP has greater antibacterial performance than the other. Based on minimum inhibitory concentration and minimum bactericidal concentration evaluations, S. aureus bacteria are more sensitive to both NPs. These nanocomposites combine the advantages of MNP and antibacterial effects, with distinctive merits including easy preparation, high inactivation capacity, and easy isolation from sample solutions by the application of an external magnetic field.Inspec keywords: nanocomposites, X‐ray chemical analysis, microorganisms, magnetic particles, scanning electron microscopy, precipitation (physical chemistry), nanomagnetics, X‐ray diffraction, X‐ray photoelectron spectra, nanoparticles, superparamagnetism, iron compounds, antibacterial activity, biomedical materials, nanomedicine, calcium compounds, nanofabrication, Fourier transform infrared spectra, magnetometers, zirconium compoundsOther keywords: antibacterial effects, antibacterial property, superparamagnetic nanoparticles, X‐ray photoelectron spectroscopy, X‐ray diffraction, X‐ray analysis, antibacterial activity, bactericidal concentration, S. aureus bacteria, Staphylococcus aureus, Escherichia coli, hydroxyapatite, coprecipitation method, scanning electron microscopy, energy dispersive X‐ray analysis, Brunauer‐Emmett‐Teller method, Fourier transform infrared spectroscopy, vibrating sample magnetometer, microbial cultivations, nanocomposites     

In Situ Synthesis of Cuprous Oxide/Cellulose Nanofibers Gel and Antibacterial Properties

Cellulose nanofibers were synthesized by acetobacter xylinum (xylinum 1.1812). The cellulose nanofibers with 30-90 nm width constructed three-dimension network gel, which could be used as a wound dressing since it can provide moist environment to a wound. However, cellulose nanofibers have no antimicrobial activity to prevent wound infection. To achieve antimicrobial activity, the cellulose nanofibers can load cuprous oxide (Cu₂O) particles on the surface. The cuprous oxide is a kind of safe antibacterial material. The copper ions can be reduced into cuprous oxides by reducing agents such as glucose, N₂H₄ and sodium hypophosphite. The cellulose nanofibers network gel was soaked in CuSO₄ solution and filled with copper ions. The cuprous oxide nanoparticles were in situ synthesized by glucose and embedded in cellulose nanofibers network. The morphologies and structure of the composite gel were analyzed by FESEM, FTIR, WAXRD and inductively coupled plasma (ICP). The sizes of Cu₂O embedded in cellulose nanofibers network are 200-500 nm wide. The peak at 605 cm⁻¹ attributed to Cu(I)-O vibration of Cu₂O shits to 611 cm⁻¹ in the Cu₂O/ cellulose composite. The Cu₂O/ cellulose nanofibers composite reveals the obvious characteristic XRD pattern of Cu₂O and the results of ICP show that the content of Cu₂O in the composite is 13.1%. The antibacterial tests prove that the Cu₂O/ cellulose nanofibers composite has the high antibacterial activities which is higher against S. aureus than against E. coli.     

Sulfamethoxazole abatement by photo-Fenton: Toxicity,inhibition and biodegradability assessment of intermediates

The objective of this work was to study the abatement of 200 mg L⁻¹ sulfamethoxazole (SMX) solution by means of photo-Fenton process. Biodegradability of the treated solutions was followed by the ratio biochemical oxygen demand at five days/chemical oxygen demand (BOD₅/COD) and toxicity by Microtox^® and inhibition tests. Experiments with different initial concentration of H₂O₂ were carried out. The initial amount of Fe²⁺ and pH of the solution were set at 10 mg L⁻¹ and 2.8 respectively. The temperature of the reactor was kept constant in all the experiments (25 ± 0.8 °C). Photo-Fenton process is thought to be a successful treatment step to improve the biodegradability of wastewater containing SMX. The complete antibiotic removal was achieved for a H₂O₂ dose over 300 mg L⁻¹. Biodegradability (BOD₅/COD) rose from zero (SMX solution) to values higher than 0.3 (treated solutions). Toxicity and inhibition tests pointed out in the same direction: oxidized intermediates for initial H₂O₂ dose over 300 mg L⁻¹ showed no toxicity effects on pure bacteria and no inhibition on activated sludge activity.     

Construction of Single‐Iron‐Atom Nanocatalysts for Highly Efficient Catalytic Antibiotics

Bacterial infection caused by pathogenic bacteria has long been an intractable issue that threatens human health. Herein, the fact that nanocatalysts with single iron atoms anchored in nitrogen‐doped amorphous carbon (SAF NCs) can effectively induce peroxidase‐like activities in the presence of H₂O₂, generating abundant hydroxyl radicals for highly effective bacterial elimination (e.g., Escherichia coli and Staphylococcus aureus), is reported. In combination with the intrinsic photothermal performance of the nanocatalysts, noticeable bacterial‐killing effects are extensively investigated. Especially, the antibacterial mechanism of critical cell membrane destruction induced by SAF NCs is unveiled. Based on the bactericidal properties of SAF NCs, in vivo bacterial infections propagated at wounds by E. coli and S. aureus pathogens can be effectively eradicated, resulting in better wound healing. Collectively, the present study highlights the highly efficient in vitro antibacterial and in vivo anti‐infection performances by the single‐iron‐atom‐containing nanocatalysts.     

Enhanced antibacterial performance of Fe<Subscript>3</Subscript>O<Subscript>4</Subscript>–Ag and MnFe<Subscript>2</Subscript>O<Subscript>4</Subscript>–Ag nanocomposites

In this work, we have described the antibacterial activities of Fe₃O₄ nanoparticles with different organic parts, including Humic acid (HA), Nicotinic acid (Nico) and Histidine (His), and the antibacterial activity of MnFe₂O₄ nanoparticles coated with PANI and SiO₂ against different bacteria and some standard antibacterial drugs. The present study revealed that the newly fabricated various Fe₃O₄ and MnFe₂O₄ nanocomposites, when combined with some different organic parts, are superiour antibacterial agents. Also, the synthesized nanocomposites can be easily separated from aqueous solution by magnetic filtration without any contamination of the medium.     

Streptomycin-modified Fe<Subscript>3</Subscript>O<Subscript>4</Subscript>–Au@Ag core–satellite magnetic nanoparticles as an effective antibacterial agent

The fabrication of ideal Ag-modified magnetic nanoparticles (MNPs) as a recyclable antibacterial agent that possesses good dispersibility, strong magnetic responsiveness, and high bactericidal activity is still a challenge. In this study, we described a simple polyethyleneimine (PEI)-assisted connection method for fabricating high-performance Au@Ag-loaded MNPs (Fe₃O₄–Au@Ag). The Fe₃O₄ cores are first modified with uniform PEI shell (2 nm) through self-assembly under sonication. And then, the negatively charged Au@Ag NPs with a uniform size of 5 nm are adsorbed on the surface of the Fe₃O₄ cores through electrostatic interaction. The Au@Ag-loaded MNPs were obtained within 30 min, and they were highly uniform in size and shape with good dispersibility and strong magnetic responsivity. With the aid of the magnetic core, the residual nanoparticles can be recycled from solution through an external magnetic field. These dense Au@Ag NPs acted as antibacterial satellites in highly active areas for Ag ion releasing and bacteria contacting. The Fe₃O₄–Au@AgMNPs exhibited good antibacterial activity against both Gram-negative and Gram-positive bacteria. Moreover, the antibacterial activity of Fe₃O₄–Au@AgMNPs was significantly improved by streptomycin antibiotic modification. Enhancement of the bactericidal efficiency of Fe₃O₄–Au@Ag-streptomycin revealed the presence of a synergistic effect between the MNPs and the introduced antibiotic.