载巯基化阿霉素的中空金纳米粒的制备与光热性能研究

目的 制备一种载阿霉素（DOX）的中空金纳米粒（HGNPs）载体。方法 合成巯基化阿霉素（DOX-SH）,通过质谱（MS ESI）和核磁共振氢谱（1H-NMR）对其结构进行表征,再将其以金硫键共价结合方式负载到中空金纳米粒表面。通过粒径、等离子共振吸收（SPR）、透射电子显微镜（TEM）、近红外（NIR）激发的光热转化实验和细胞毒性实验对制备的中空金纳米粒载药体系进行评价。结果 质谱显示,合成的巯基化阿霉素的分子量为616,核磁共振氢谱所示的结构也与目标产物相符。阿霉素-中空金纳米粒复合载药体系(HGNPs-DOX)的粒径为70 nm左右;等离子共振吸收最大吸收波长为800 nm左右,具有良好的光热转化能力;透射电子显微镜显示,其为中空圆球形结构,壳厚4~6 nm;细胞毒性显示,在高浓度时,阿霉素-中空金纳米粒复合载药体系能显著减小阿霉素的毒性。结论 成功合成了阿霉素-中空金纳米粒复合载体,其具有良好的结构,良好的光热转化能力,较小的细胞毒性,未来可成为有研究前景的新一代化疗联合光热治疗的递送载体。     

金纳米粒及其在药物传递系统中的应用研究进展

近年来,随着纳米材料科学的蓬勃发展,金纳米粒由于具有独特的光学和物理性质以及毒性小、比表面积大、表面可功能化修饰、易与药物分子结合等特点,其作为载体在药物传递系统中的应用已引起广泛关注。综述金纳米粒的特性、合成方法、体内分布与毒性以及在不同药物传递系统中的应用研究。     

抗 EGFR 单克隆抗体偶联载紫杉醇纳米粒对胃癌肿瘤靶向性能力研究

目的：为了增强载药纳米粒靶向肿瘤的能力,将载药纳米粒与抗上皮生长因子细胞增殖和信号传导受体（EGFR）单克隆抗体偶联,探究该偶联是否会增加胃癌肿瘤靶向性。方法将制备好的载药纳米粒在羟基胶乳微球偶联抗体（EDC）的作用下通过酰胺反应与抗 EGFR 单克隆抗体进行偶联,制备成载药免疫纳米粒。通过透析袋法测定纳米粒体外缓释效果,用 ELISA 法测定抗体与载药纳米粒偶联率,最后采用荧光标记法对胃癌模型鼠进行活体成像结果纳米粒表面光滑,分布均匀,粒径在200～300 nm 间,载药量为61．02％,并且具有缓慢释药的效果,抗体与载药纳米粒的偶联率达到了70％,最终荧光活体成像的结果显示,此免疫载药抗体具有靶向胃肿瘤的效果。结论我们制备的免疫纳米粒既可以缓释药物也存在一定肿瘤靶向性,所以将抗体与载药纳米粒偶联,可以增加肿瘤病灶处局部的药物浓度,以此来缓解抗肿瘤药物对人体其他正常组织毒副作用。     

基于丝素蛋白的纳米粒药物递送系统研究进展

丝素蛋白(silk fibroin, SF)是一种天然高分子,具有一定的水溶性、结构修饰性、良好的生物相容性和生物降解性,可作为药物递送的载体材料。SF载药纳米粒可控制药物释放、减少不良反应、提高治疗效果,是一种有前景的药物递送系统。本综述介绍了SF的基本特征、SF载药纳米粒的制备方法和SF在纳米粒药物递送系统的应用,在此基础上,对SF载药纳米粒的进一步发展进行了展望。     

银模板法制备中空金纳米粒及其质量评价

目的 制备并表征一种可用于载药的中空金纳米粒载体.方法 以银纳米粒为模板,通过模板置换法使氯金酸与银纳米粒反应生成金壳,并裹覆于银纳米粒表面,最后形成一种中空结构的金纳米粒,通过单因素考察对中空金纳米粒的制备进行初步探究.使用透射电镜对中空金纳米粒进行结构观察,紫外全波长扫描考察其吸收情况,体外光热转化试验考察载体的光热转化能力,以及四甲基偶氮唑蓝(MTT)试验考察载体细胞毒性.结果 氯金酸的加入方式为逐滴加入,制备温度为60 ℃,氯金酸(25 mmol·L-1)的加入量为128 μL,中空金纳米的粒径为35~55 nm,壳厚4~6 nm,最大吸收波长750~800 nm,具备较强的光热转化能力.细胞毒性结果表明,中空金纳米粒对人皮肤成纤维细胞(HDF)没有明显的细胞毒性.结论 经过优化制备得到的中空金纳米粒具备较好的中空结构,以及优异的光热转化能力和较低的细胞毒性.     

阿苯达唑聚氰基丙烯酸正丁酯纳米粒的制备、性质及其组织靶向性研究阿苯达唑聚氰基丙烯酸正丁酯纳米粒的制备、性质及其组织靶向性研究

目的制备阿苯达唑聚氰基丙烯酸正丁酯纳米粒（albendazole polybutycyanocrylate nanoparticles，ABZ-PBCA-NP）TDDS给药系统，并考察相关特性及组织分布靶向性。方法种子乳化聚合法制备阿苯达唑纳米粒；等温吸附法考察纳米粒载药特性；动态透析法研究4种制剂的体外释药动力学；同位素标记阿苯达唑纳米粒在小鼠脏器组织分布和生物利用度。结果ABZ-PBCA-NP体外释药遵循Higuchi方程，加入PVP制成的载药纳米粒符合双指数函数。纳米粒的载药方式遵循Langmuir吸附方程。小鼠ig ³H-ABZ-PBCA-NP后, 药物的肝、脾中的靶向指数分别为11.4和3.9，阿苯达唑纳米粒和混悬剂相对生物利用度分别为76.0%和36.9%。结论制备纳米粒加入PVP可使药物具吸附性和分散性，纳米粒载体可降低药物与血浆蛋白结合率，增强药物的肝、脾脏器靶向性和延缓释药。     

不同载药方法对介孔二氧化钛纳米粒载药及药物溶出速率的影响

目的考察不同载药方法对介孔二氧化钛纳米粒载药系统载药和溶出速率的影响。方法通过溶剂挥干法、熔融法、吸附平衡法分别将卡维地洛包载于介孔二氧化钛纳米粒中,用扫描电镜和透射电镜观测样品形貌,氮气吸附-解吸法测量载体的比表面积和孔体积,差示扫描量热法分析药物粒子的存在状态,X-射线衍射法进行物相分析,热失重法分析载药量,最后测定载药系统的溶出速率并进行长期稳定性试验。结果三种载药方法均能通过改变药物的存在状态使药物以非晶型存在于载体中而达到提高溶出速率的目的。其中溶剂挥干法所得的载药系统溶出速率提高显著,并且更具有长期稳定性。结论溶剂挥干法为介孔二氧化钛纳米粒载药的首选。     

载奥沙利铂的还原敏感型四氧化三铁纳米粒的体内外靶向性评价

化疗药物的非特异性蓄积和释放是影响其治疗效果以及引起不良反应的主要原因。现阶段,将药物纳米制剂化并且进行响应性释药设计是提高药物肿瘤特异性蓄积量和降低其不良反应的重要策略。本研究首先合成了一种α-烯醇化酶靶向肽修饰的共价荷载奥沙利铂前药的聚乙二醇聚赖氨酸嵌段共聚物,通过相转透析法制备了载药聚合物包覆的四氧化三铁纳米粒,以提高奥沙利铂的循环稳定性及肿瘤靶向性。在体外和活体水平对靶向修饰的载药四氧化三铁纳米粒的物理化学性质、还原响应药物释放、细胞摄取和肿瘤靶向等生物学功能进行了相关研究。体外的还原响应释药、肿瘤靶向摄取及摄取抑制考察结果显示,在模拟肿瘤细胞浆微环境的还原条件中,载药纳米粒可实现3 h内超80%的奥沙利铂原型药物的快速释放;流式细胞术的结果显示,靶向多肽的修饰能够增加肿瘤细胞对载药纳米粒的摄取量,并且靶向载药纳米粒主要是通过受体蛋白和小窝蛋白介导的能量依赖的内吞途径被肿瘤细胞所摄取的。所有动物实验操作均通过复旦大学药学院实验动物伦理委员会批准并遵循相关管理规定。药物动力学实验结果显示,纳米制剂化能显著增加奥沙利铂的平均药时曲线下面积(AUC_0-∞),约为...     

葫芦素B-聚乳酸-羟基乙酸共聚物载药纳米粒的构建与药效学评价

目的 以聚乳酸-羟基乙酸共聚物（PLGA）作为纳米制剂载体材料将葫芦素B制备成纳米粒,并考察其对HepG2肝癌细胞的抑制效果。方法 使用乳化溶剂蒸发法制备葫芦素B-PLGA载药纳米粒,以PLGA浓度（X₁）、PVA浓度（X₂）和药物浓度（X₃）作为考察因素,以载药纳米粒的粒径大小（Y₁）和包封率（Y₂）作为评价指标,应用中心复合设计-效应面法优化葫芦素B-PLGA载药纳米粒处方;测定了纳米粒的粒径分布和Zeta电位值,通过透射电镜观察其微观形态,并考察了葫芦素B-PLGA载药纳米粒的体外药物释放特性;比较了葫芦素B与葫芦素B-PLGA载药纳米粒对HepG2肝癌细胞的抑制效果。结果 葫芦素B-PLGA载药纳米粒的最优处方组成为：PLGA浓度为9.0%,PVA浓度为2.0%,药物浓度为4.5%,制备的纳米粒粒径为（145.4±15.8） nm,Zeta电位值为（-7.6±0.8） mV;透射电镜下可观察到纳米粒表面光滑,分布均匀;葫芦素B-PLGA载药纳米粒释药前期出现突释,后期平缓,48 h药物释放达到86%;葫芦素B-PLGA载药纳米粒对HepG2肝癌细胞的抑制作用显著高于葫芦素B。结论 葫芦素B-PLGA载药纳米粒可延缓药物释放,提高对HepG2肝癌细胞的抑制活性,为进一步临床研究奠定实验基础。     

壳聚糖载药纳米粒研究进展

目的介绍壳聚糖载药纳米粒近年来的研究进展。方法总结壳聚糖纳米粒的制备方法、释药特性、生物摄取及其应用。结果不同的制备方法可得到不同粒径和表面特性的壳聚糖纳米粒。壳聚糖纳米粒改变了壳聚糖的摄取机制，广泛应用于药物的器官靶向、DNA转染效率提高、药物的非注射途释给药等方面。结论壳聚糖纳米粒作为一种新型的药物载体，具有重要的研究开发价值。     

Drug delivery vectors based on filamentous bacteriophages and phage-mimetic nanoparticles

With the development of nanomedicine, a mass of nanocarriers have been exploited and utilized for targeted drug delivery, including liposomes, polymers, nanoparticles, viruses, and stem cells. Due to huge surface bearing capacity and flexible genetic engineering property, filamentous bacteriophage and phage-mimetic nanoparticles are attracting more and more attentions. As a rod-like bio-nanofiber without tropism to mammalian cells, filamentous phage can be easily loaded with drugs and directly delivered to the lesion location. In particular, chemical drugs can be conjugated on phage surface by chemical modification, and gene drugs can also be inserted into the genome of phage by recombinant DNA technology. Meanwhile, specific peptides/proteins displayed on the phage surface are able to conjugate with nanoparticles which will endow them specific-targeting and huge drug-loading capacity. Additionally, phage peptides/proteins can directly self-assemble into phage-mimetic nanoparticles which may be applied for self-navigating drug delivery nanovehicles. In this review, we summarize the production of phage particles, the identification of targeting peptides, and the recent applications of filamentous bacteriophages as well as their protein/peptide for targeting drug delivery in vitro and in vivo. The improvement of our understanding of filamentous bacteriophage and phage-mimetic nanoparticles will supply new tools for biotechnological approaches.     

基于纳米金的肿瘤靶向给药系统的研究进展

化疗是目前临床癌症治疗的主要手段之一，主要通过静脉给药细胞毒药物，在杀伤肿瘤细胞的同时，往往会导致健康器官和组织的全身细胞毒性。最新研究表明，纳米金是一种高效的抗肿瘤药物载体，能够携带药物穿透血管和组织屏障进入肿瘤病灶，并特异性积蓄于肿瘤组织，有效降低化疗药物的机体不良反应。此外，金纳米粒子具有易修饰性，相比于其他纳米粒子，较易与多种化合物、蛋白、多肽、核酸等偶联，在肿瘤治疗、成像等方面具有独特的应用优势。本文综述了金纳米粒子在肿瘤靶向递送方向的最新研究进展，并阐述了其在表面修饰、靶向策略和生物安全性等方面的优势和不足。     

Gold nanoparticles: an era in bionanotechnology

Introduction: Gold nanoparticles have been efficiently and effectively used for the delivery of biomolecules and genes along with the potential to offer extremely sensitive diagnostics and imaging methods.

Areas covered: This review discusses the historical aspects, synthesis of gold nanoparticles, gold nanoparticles as drug delivery vehicles, photothermal effect of gold nanoparticles and the applications of gold nanoparticles. Gold nanoparticles with their unique optical properties may be useful as biosensors in living cells and has application in the field of drug delivery and photothermal therapy. Depending on the size, shape and degree of aggregation and nature of the protecting organic shells on their surface, gold nanoparticles can appear red, blue and other colors and emit bright resonance light of various wavelengths, which falls under visible region. Because of this property, gold nanoparticles have been extensively used as probes for sensing/imaging a wide range of analysts/targets such as proteins, cells and nucleic acids.

Expert opinion: Gold nanoparticles provide an admirable platform for the delivery of biomolecules and genes.     

Quenching-induced deactivation of photosensitizer by nanoencapsulation to improve phototherapy of cancer

Photodynamic therapy has emerged as a promising alternative to current cancer treatment. However, conventional photosensitizers have several limitations due to their unsuitable pharmaceutical formulations and lack of selectivity. Our strategy was to exploit the advantages of nanoparticles and the quenching-induced deactivation of the model photosensitizer hypericin to produce “activatable” drug delivery systems. Efficient fluorescence and activity quenching were achieved by increasing the drug-loading rate of nanoparticles. In vitro assays confirmed the reversibility of hypericin deactivation, as the hypericin fluorescence and photodynamic activity were recovered upon cell internalization.     

受体介导的肝靶向载药系统研究进展

介绍近几年已报道的有关受体介导的肝靶向载药系统的研究情况。近年来受体介导的肝靶向载药系统的研究取得了一些可喜进展,相关配体-受体可与药物、脂质体、纳米粒、基因、偶联物等相连,提高药物或载体的肝靶向能力。受体介导机制在肝靶向载药系统的研究领域具有广阔的应用前景,尤其是肝脏特异性受体的不断发掘,丰富了肝主动靶向的理论体系,展示了肝脏疾病治疗的美好未来。     

Review on gold nanoparticles and their applications

Gold nanoparticles are widely used in many fields as preferred materials for their unique optical and physical properties, such as surface plasmon oscillations for labeling, imaging, and sensing. Recently, many advancements were made in biomedical applications with better biocompatibility in disease diagnosis and therapeutics. Au-NPs could be prepared and conjugated with many functionalizing agents, such as polymers, surfactants, ligands, dendrimers, drugs, DNA, RNA, proteins, peptides and oligonucleotides. This review addressed the use of gold nanoparticles and the surface functionalization with a wide range of molecules, expanding and improving gold nanoparticles in targeting drugs for photothermal therapy with reduced cytotoxic effcts in various cancers, gene therapy and many other diseases. Overall, Au-NPs would be a promising vehicle for drug delivery and therapies.     

Development of gentamicin-gold nanospheres for antimicrobial drug delivery to Staphylococcal infected foci

Abstract

Even though the therapeutic efficacy of numerous antimicrobial drugs has been well established, inefficient delivery can result in an inadequate therapeutic index. Gold nanoparticles have unique physicochemical properties such as large surface area to mass ratio and functionalizable structure. These properties can be applied to facilitate the administration of antimicrobial drugs, thereby overcoming some of the limitations in traditional antimicrobial therapeutics. In this study, gold nanospheres were used as a drug carrier system for gentamicin delivery to Staphylococcal infected foci. Conjugation of gentamicin with gold nanospheres was performed in HEPES buffer. The attachment of gentamicin to gold nanospheres was confirmed by UV/Vis spectroscopy. The HPLC and atomic absorption spectrometer analyses showed that 347 gentamicin molecules were attached to each gold nanosphere. Minimum inhibitory concentration and minimum bactericidal concentration studies showed the enhanced antibacterial effect of gentamicin-gold nanospheres complex in comparison with free gentamicin. The biodistribution study showed the localization of the complex at the site of Staphylococcal infection foci with high sensitivity in mouse model.     

Inorganic nanoparticles for hydrophobic anticancer drug delivery

OBJECTIVE Many drug candidates identified from natural products are poorly water-soluble.The surfactants used to disperse the hydrophobic anticancer drugs in water may cause a serious of acute hypersensitivity reactions.Nanotechnology provides an alternative strategy for delivery of anticancer drugs.In the present study,different inorganic nanoparticles are utilized as hydrophobic anticancer drug carriers.METHODS Different inorganic superparamagnetic iron oxide,platinum and gold nanoparticles were synthesized.The hydrophobic anticancer drugs such as curcumin,gambogic acid and doxorubicin(DOX)base were loaded into the porous area or onto the surface of the nanoparticles.Cellular uptake and biocompatibility of nanoparticles were studied in human glioblastoma U-87 MG cells.The anticancer effect of drug loaded nanoparticles was compared with that of free drugs.Photothermal conversion of platinum and gold nanoparticles was studied by irradiation of nanoparticles with a near-infrared laser.RESULTS The synthesized nanoparticles are readily internalized by U-87 MG cells,and the internalized nanoparticles are mainly localized in endosomes/lysosomes in cells.The nanoparticle-based drug carrier provides the aqueous dispersions of the hydrophobic drugs.In endosomes/lysosomes mimicking buffers with a pH of 4.5-5.5,pH-dependent drug release was observed from drug loaded nanoparticles.The intracellular drug content and cytotoxicity are significantly higher for drug loaded nanoparticles than free drug.Photothermal treatment has a synergistic effect on drug′s anticancer activity.CONCLUSION These results suggested inorganic nanoparticles is a promising intracellular carrier for hydrophobic anticancer drugs.     

Nanostructured materials in drug and gene delivery: a review of the state of the art

A wide variety of drug delivery systems have been developed, each with its own advantages and limitations, but the important goals of all of the systems are to enhance bioavailability, reduce drug toxicity, target to a particular organ, and increase the stability of the drug. The development of nanostructured drug carriers have grasped increased attention from scientific and commercial organizations due to their unique ability to deliver drugs and challenging molecules such as proteins and nucleic acids. These carriers present many technological advantages such as high carrier capacity, high chemical and biological stability, feasibility of incorporating both hydrophilic and hydrophobic substances, and their ability to be administered by a variety of routes (including oral, inhalational, and parenteral) to provide controlled/sustained drug release. Moreover, applications of nanoparticulate formulations in enhancing drug solubility, dissolution, bioavailability, safety, and stability have already been proven. In the view of their multifaceted applications, the present review aims to discuss and summarize some of the interesting findings and applications, methods of preparation, and characterization of various nanostructured carriers useful in drug delivery. Included in this discussion are polymeric nanoparticles, solid lipid nanoparticles, nanostructured lipid carriers, dendrimers, cyclodextrins, fullerenes, gold and silica nanoparticles, and quantum dots. Because there are likely to be new applications for nanoparticles in drug delivery, they are expected to solve many problems associated with the delivery of drugs and biomolecules through different delivery routes.