介孔二氧化硅纳米材料的皮肤安全性研究

目的:评价介孔二氧化硅纳米材料(MSNs)的皮肤渗透性、刺激性及过敏性。方法:在体透皮实验中,将分别载不同量(0.75%和3%,W/W)MSNs和氨基修饰的MSNs(NH2-MSNs)的凝胶涂布于大鼠背部皮肤,考察24 h后皮肤中硅含量及在皮肤组织中的分布(n=4);皮肤刺激性实验中,将分别载3%MSNs和NH2-MSNs的凝胶多次(1次/d,共7 d)涂布于家兔完整皮肤及破损皮肤,采用同体左右侧自身对照,给药期间每日观察局部皮肤红斑及水肿情况(n=4);皮肤过敏性实验中,于实验第1、7、14天将载3%MSNs和NH2-MSNs的凝胶、凝胶基质和1%2,4-二硝基氯代苯溶液(阳性对照)分别涂布于豚鼠背部皮肤左侧致敏,于末次致敏后14 d(第28天)同法涂药于右侧激发接触,以是否出现红斑或水肿为指标,观察局部皮肤的过敏反应(n=6)。结果:载0.75%、3%MSNs的凝胶致皮肤中硅含量分别为(10.812±3.963)、(22.050±5.721)μg/g,载0.75%、3%NH2-MSNs的凝胶致皮肤中硅含量分别为(7.799±2.068)、(16.416±3.221)μg/g,透射电镜显示MSNs能跨过皮肤屏障,进入真皮层;完整皮肤和破损皮肤均未出现红斑或水肿现象;与阳性对照比较,载MSNs及NH2-MSNs的凝胶均未导致豚鼠皮肤出现红斑或水肿。结论:MSNs作为局部施药载体具有良好的皮肤安全性。     

介孔硅材料提高难溶性药物生物利用度的研究进展

介孔二氧化硅作为近年来比较热门的无机介孔载体材料,因其具有孔道排列规整、水热稳定性良好、生物相容性好,可以储存药物并保持药物的无定形态等特点,非常适合装载水难溶性药物。本文通过查阅国内外的相关文献,就难溶性药物口服生物利用度低的原因进行分析,并归纳总结了国内外关于介孔二氧化硅载体提高难溶性药物生物利用度方面的最新研究进展,为设计和制备具有特定结构和性能的介孔二氧化硅载体,提高难溶性药物的生物利用度及其临床应用提供参考。     

用于光热治疗的金／介孔纳米材料的制备与研究

目的：研究金纳米颗粒包覆的介孔硅二氧化硅（MSN＠Au）的制备方法,合成后的MSN＠Au纳米材料具有光热抗肿瘤作用。方法以材料对卵巢癌（Hela）细胞的抑制率作为评价指标,综合考察自制的纳米材料的抗肿瘤作用。结果合成的MSN纳米颗粒粒径均一、分散性良好,均匀吸附金纳米颗粒后的材料利用808 nm NIR照射3 min后,癌细胞存活率只有50％以下。结论制备出的MSN＠Au纳米材料,利用NIR照射后,能在肿瘤细胞局部产热,杀伤肿瘤细胞,对肿瘤细胞有热疗作用。     

纳米材料的生物效应研究进展

目的了解纳米材料的研究背景、国内外发展现状和趋势以及纳米材料的生物效应、纳米材料的修饰改造,为更安全地使用纳米材料提供科学依据。方法查阅相关文献,及其网上背景资料进行总结。结果发现纳米材料有正效应也有负效应。结论若能很好降低纳米尺度物质的生物效应或毒性,可以创造更高的经济价值。     

生物分子模板功能化纳米材料的研究进展

随着纳米科技的快速发展,纳米材料得到了广泛的应用,性质也得到了全面的发挥.科学家在对生物矿化分子进行充分研究的基础上,发现利用蛋白质、多肽、DNA、RNA、多糖等生物分子作为模板进行功能化无机纳米材料的设计和制备是一种有效和可行的方法.基于生物分子制备的纳米材料具有几何尺寸高度均一、结构多样、稳定性良好、制备过程环保等特性,因此近些年来成为研究的热点,同时合成出的材料具有很好的应用前景.本文主要对近年来利用生物分子为模板的纳米材料制备方法、材料实际应用以及所涉及的应用机理等方面的研究进行了综述.     

介孔二氧化硅纳米粒的研究进展

介孔二氧化硅纳米粒(MSNs)具有良好生物相容性、有序介孔结构、比表面积大、表面易修饰性等特点,在很多生物医药领域显示出了极大的应用前景,尤其是基于MSNs的纳米药物输送体系被广泛用于各种药物的递送。主要介绍MSNs和可降解MSNs的制备,同时介绍了MSNs膜包被及官能团修饰在缓释控释药物中的应用,最后探讨了MSNs递进到中空介孔二氧化硅纳米粒(HMSNs)的更大的应用前景。     

介孔二氧化硅纳米粒介导的药物传递系统及其生物安全性的研究进展

介孔二氧化硅纳米粒(MSNs)是一种新型无机纳米材料,因具有独特的网状孔道结构、巨大的比表面积、孔径分布窄且可调节及易于表面修饰等特性,已用于药物控释系统的研究.MSNs载体的药物负载量与其介孔容积相关,表面经修饰后可实现药物的控释和靶向传递.然而,随着MSNs载体与人体接触的机会和时间日益增加,其安全性也受到广泛关注.本文综合近10年来国内外的相关文献,归纳了MSNs在递药系统中的应用,并分析了其生物安全性的影响因素.     

载姜黄素的介孔二氧化硅及中空介孔二氧化硅的制备及释药性能研究

目的:制备载姜黄素(Cur)的介孔二氧化硅(MSN)和中空介孔二氧化硅(HMSN),并考察其体外释药行为.方法:采用溶胶-凝胶法、选择性刻蚀法分别制备MSN和HMSN,并采用溶剂挥干法制备载药体系Cur-MSN、Cur-HMSN,以紫外分光光度法测定其载药量.采用差示扫描量热法(DSC)和X射线衍射法(XRD)表征药物...     

铜掺杂介孔硅载双硫仑抗肠癌活性研究

目的 以铜掺杂介孔硅（Cu/MSNs）为载体包载双硫仑（DSF）制备成纳米粒,研究其对CT.26WT肠癌细胞的体外抑制活性。方法 Stober法制备二氧化硅微粒后对其进行优化,MTT法验证其体外抗肿瘤活性。结果 通过单因素法优化得到在1.5 mL氨水、12.5 mL水和温度85 ℃时具有最佳粒径;MTT法得到DSF、5-Fu和DSF-NPs在48 h下的IC₅₀值分别为7.532、3.359和1.208 μg·mL^-1,72 h的IC50值分别为2.258、1.137和0.985 μg·mL^-1。结论 铜掺杂介孔硅能有效的负载双硫仑并增强其抗肠癌细胞活性,具有优良的抗肠癌潜力。     

Nanostructure-loaded mesoporous silica for controlled release of coumarin derivatives: A novel testing of the hyperthermia effect

The synthesis of three types of mesoporous materials is reported: pure mesoporous silica (MCM-41), a nanocomposite of mesoporous silica with hydroxyapatite (MCM-41-HA) and mesoporous silica/gold nanorods nanocomposite (MCM-41-GNRs). The mesoporous materials were characterized by X-ray diffraction, N₂ adsorption isotherms, FTIR spectroscopy, transmission electron microscopy, and scanning electron microscopy. The samples were loaded with coumarin thiourea derivatives (I-IV) having functional groups of varying sizes and the in vitro release assays were monitored, and the release behavior was investigated as a function of soaking time in simulated body fluid. Two release stages were obtained in MCM-41, MCM-41-HA and MCM-41-GNRs loaded samples with the early release stages accounting for about 30% of loaded derivatives. These early release stages are characterized by Higuchi rate constant values nearly twice the values associated with the second release stages. The influence of substituent size on the release rate constants was explained in terms of sorption sites and hydrogen bonding with silanol groups on silicates. The release of coumarin derivatives loaded on MCM-41, MCM-41-HA and MCM-41-GNRs occurs over remarkably long time of the order of about 260 h with faster release rates in loaded MCM-41 and MCM-41-GNRs samples compared with MCM-41-HA ones. The role of hyperthermia effect in enhancing release rates was investigated by subjecting loaded MCM-41-GNRs to near infrared (NIR) radiation at 800 nm. This would be of significance in targeted drug release using hyperthermia effect. Unlike hydroxyl apatite, loading MCM-41 with gold nanorods does not affect the release kinetics. Only when these samples are irradiated with NIR photons, does the release occur with enhanced rates. This property could be valuable in selected targeting of drugs.     

Research progress of the engagement of inorganic nanomaterials in cancer immunotherapy

Cancer has attracted widespread attention from scientists for its high morbidity and mortality, posing great threats to people’s health. Cancer immunotherapy with high specificity, low toxicity as well as triggering systemic anti-tumor response has gradually become common in clinical cancer treatment. However, due to the insufficient immunogenicity of tumor antigens peptides, weak ability to precisely target tumor sites, and the formation of tumor immunosuppressive microenvironment, the efficacy of immunotherapy is often limited. In recent years, the emergence of inorganic nanomaterials makes it possible for overcoming the limitations mentioned above. With self-adjuvant properties, high targeting ability, and good biocompatibility, the inorganic nanomaterials have been integrated with cancer immunotherapy and significantly improved the therapeutic effects.     

In vivo near infrared fluorescence imaging and dynamic quantification of pancreatic metastatic tumors using folic acid conjugated biodegradable mesoporous silica nanoparticles

Cancer metastasis is one of the biggest challenges in cancer treatments since it increases the likelihood that a patient will die from the disease. Therefore, the availability of techniques for the early detection and quantification of tumors is very important. We have prepared cyanine 7.5 NHS ester (Cy_7.5) and folic acid (FA) conjugated biodegradable mesoporous silica nanoparticles (bMSN@Cy_7.5-FA NPs) (~100 nm) for visualizing tumors in vivo. The fluorescence spectra revealed that the emission peak of bMSN@Cy_7.5-FA NPs had a red-shift of 1 nm. Confocal immunofluorescent images showed that bMSN@Cy_7.5-FA NPs had an excellent targeting ability for visualizing cancer cells. In vivo fluorescence imaging has been conducted using an orthotopic model for pancreatic cancer within 48 h, and the fluorescence intensity reached a maximum at a post injection time-point of 12 h, which demonstrated that the use of bMSN@Cy_7.5-FA NPs provides an excellent imaging platform for tumor precision therapy in mice.     

Characterization of modified mesoporous silica nanoparticles as vectors for siRNA delivery

 Gene therapy using siRNA molecules is nowadays considered as a promising approach. For successful therapy, development of a stable and reliable vector for siRNA is crucial. Non-viral and non-organic vectors like mesoporous silica nanoparticles (MSN) are associated with lack of most viral vector drawbacks, such as toxicity, immunogenicity, but also generally a low nucleic acid carrying capacity. To overcome this hurdle, we here modified the pore walls of MSNs with surface-hyperbranching polymerized poly(ethyleneimine) (hbPEI), which provides an abundance of amino-groups for loading of a larger amount of siRNA molecules via electrostatic adsorption. After loading, the particles were covered with a second layer of pre-polymerized PEI to provide better protection of siRNA inside the pores, more effective cellular uptake and endosomal escape. To test the transfection efficiency of PEI covered siRNA/MSNs, MDA-MB 231 breast cancer cells stably expressing GFP were used. We demonstrate that PEI-coated siRNA/MSN complexes provide more effective delivery of siRNAs compared to unmodified MSNs. Thus, it can be concluded that appropriately surface-modified MSNs can be considered as prospective vectors for therapeutic siRNA delivery.     

Endosomal escape kinetics of mesoporous silica-based system for efficient siRNA delivery

The strategy of encapsulating small interference RNA (siRNA) into the mesopores enables mesoporous silica nanoparticles (MSNs) to be an attractive material for siRNA delivery. Nevertheless, the gene silencing efficiency mediated by this sort of vehicles has not been systematically investigated yet. In this work, through quantifying gene silencing efficiency by flow cytometry (FCM) and performing intracellular tracking by confocal laser scanning microscopy (CLSM), we found that the RNA interference (RNAi) efficiency mediated by MSNs-based delivery vehicles was strongly dependent on their endosomal escape capability. Thereafter, we investigated the correlation between the gene knockdown efficiency and the endosomal escape kinetics of such carriers. The results indicated that highly efficient MSNs-based siRNA delivery vectors must possess the capability of initiating effectively endosomal escape before the degradation of their packaged siRNA in endolysosomes.     

Mussel-inspired polydopamine coated mesoporous silica nanoparticles as pH-sensitive nanocarriers for controlled release

A novel pH-sensitive controlled release system is proposed by using mussel-inspired polydopamine (PDA) coated mesoporous silica nanoparticles (MSNs) as nanocarriers. MSNs with a large pore diameter are synthesized by using 1,3,5-trimethylbenzene as a pore-expanding agent and are modified with a PDA coating by virtue of oxidative self-polymerization of dopamine in neutral pH. PDA coated MSNs are characterized by FTIR, TEM, N₂ adsorption and XPS techniques. The PDA coating can work as pH-sensitive gatekeepers to control the release of drug molecules from MSNs in response to the pH-stimulus. Doxorubicin (DOX, an anticancer drug) can be released in the acid media and blocked in the neutral media.     

Preparation and characterization of mesoporous silica nanoparticles with enlarged pores capped with crosslinked PEI

The epidemiological statistics reveals the striking patterns of cancer in women and highlights the need for novel therapeutic strategies. In this work, mesoporous silica nanoparticles (MSNs) as representative of inorganic nanoparticles were prepared for loading siRNA that plays a role of gene silencing to treat breast carcinoma (MCF-7) cells. The critical processes of synthesis were optimized for the nanoparticles with desired quality attributes that have the enlarged pores for elevated loading capacity.After siRNA loading into mesoporous, crosslinked-polyethylenimine was employed as the cap to coat the enlarged MSN pores and protect the cargo from leakage. The elevated quantity of siRNA (35 μg siRNA/mg MSNs) were loaded in the MSNs. The as-synthesized MSNs were further evaluated on MCF-7 cells in vitro and shown negligible cytotoxicity.As expected, the siRNA loaded in the as-synthesized MSNs was readily internalized into MCF-7 cells and displayed 420 times higher intake than that of naked siRNA. The MSNs may be exploited to become an effective siRNA cell delivery strategy and further studied for the anti-tumor efficacy.     

Preparation of a mesoporous silica-based nano-vehicle for dual DOX/CPT pH-triggered delivery

A dual doxorubicin/camptothecin (DOX/CPT) pH-triggered drug delivery mesoporous silica nanoparticle (MSN)-based nano-vehicle has been prepared. In this drug-delivery system (DDS), CPT is loaded inside the pores of the MSNs, while DOX is covalently attached to the surface of an aldehyde-functionalized MSN through a dihydrazide–polyethylene glycol chain. Thus, DOX and the linker act as pH-sensitive gatekeeper. The system is versatile and easy to assemble, not requiring the chemical modification of the drugs. While at physiological conditions the release of the drugs is negligible, at acidic pH a burst release of DOX and a gradual release of CPT take place. In vitro cytotoxicity tests have demonstrated that this DDS can deliver efficiently DOX and CPT for combination therapy.