磁性纳米粒子在肝细胞癌磁共振成像及靶向治疗方面的研究进展

超顺磁性纳米粒子作为新型材料在临床领域应用广泛,如医学成像及诊断、药物靶向治疗、磁热疗等。它不仅可以在肝细胞癌（HCC）的早期作出特异性诊断,更是一种理想的靶向药物纳米载体。介绍了磁性纳米粒子作为靶向药物载体的性质特点、磁共振成像原理、靶向HCC的作用机制等,重点介绍了磁性纳米粒子的表面修饰及功能化,及其在主动靶向药物输送系统中的应用。认为磁性纳米粒子的应用必将在HCC的诊治中发挥更大的作用。     

Cationic solid–lipid nanoparticles are as efficient as electroporation in DNA vaccination against visceral leishmaniasis in mice

The use of an appropriate delivery system has recently emerged as a promising approach for the development of effective vaccination against visceral leishmaniasis (VL). Here, we compare two vaccine delivery systems, namely electroporation and cationic solid–lipid nanoparticle (cSLN) formulation, to administer a DNA vaccine harbouring the L. donovani A2 antigen along with L. infantum cysteine proteinases [CPA and CPB without its unusual C‐terminal extension (CPB^?CTE)] and evaluate their potential against L. infantum challenge. Prime‐boost administration of the pcDNA‐A2‐CPA‐CPB^?CTE delivered by either electroporation or cSLN formulation protects BALB/c mice against L. infantum challenge and that protective immunity is associated with high levels of IFN‐γ and lower levels of IL‐10 production, leading to a strong Th1 immune response. At all time points, the ratio of IFN‐γ: IL‐10 induced upon restimulation with rA2‐rCPA‐rCPB and F/T antigens was significantly higher in vaccinated animals. Moreover, Th2‐efficient protection was elicited through a high humoral immune response. Nitric oxide production, parasite burden and histopathological analysis were also in concordance with other findings. Overall, these data indicate that similar to the electroporation delivery system, cSLNs as a nanoscale vehicle of Leishmania antigens could improve immune response, hence indicating the promise of these strategies against visceral leishmaniasis.     

环孢素A白蛋白纳米粒的制备、体外释放及大鼠药代动力学评价

以人血白蛋白为载体,制备环孢素A白蛋白纳米粒(CyA-HSA),考察其包封率、载药量、粒径、Zeta电位、pH、渗透压、形态、稀释稳定性等理化性质,并以透析法研究其体外释药特性。结果表明,所制得的CyA-HSA纳米粒载药量为14.7%,包封率为85.8%,动态光散射法测定其粒径为240.5 nm,Zeta电位为-32.0 mV,pH为7.0,渗透压为314.7 mOsmol/kg。透射电镜照片表明该纳米体系为规整的球形结构。CyA-HSA纳米制剂比市售环孢素A注射剂(山地明)具有更优越的稀释稳定性,且二者皆具有缓释特性,并呈现零级释药特征。CyA-HSA和山地明注射剂同剂量(7 mg/kg)静脉注射后,二者体内过程均符合二房室模型,与山地明注射剂相比,CyA-HSA的药物清除率和药物从中央室的消除速率常数k₁₀均有显著下降,AUC显著提高(P<0.05)。HSA 纳米粒能够高效负载CyA,同时克服了山地明注射剂中增溶剂(聚氧乙烯蓖麻油)的不良反应,有望开发成为环孢素的新一代制剂。     

人胃癌细胞HGC-27对PEG化聚乳酸羟基乙酸纳米粒的摄取

制备黏惰性纳米粒(mPEG-PLGA-NPs)以克服人胃癌HGC-27细胞周围黏液的黏附,研究mPEG-PLGA-NPs理化性质对纳米粒穿透黏液被HGC-27细胞摄取的影响。体外黏蛋白黏附实验证明,mPEG-PLGA-NPs具有良好的黏惰性;激光共聚焦显微镜及HPLC法考察HGC-27细胞对不同理化性质mPEG-PLGA-NPs的摄取。结果显示:HGC-27细胞对纳米粒的摄取与孵育时间(0~4 h)成依赖关系。同一孵育时间内,HGC-27细胞对纳米粒的摄取随着mPEG相对分子质量和修饰密度的增加而增加,10%PEG₂₀₀₀-PLGA-NPs的摄取量是PLGA-NPs的1.7~2.0倍,是荷正电荷CS-PLGA-NPs的摄取量的1.8~2.4倍,粒径400 nm 的纳米粒的摄取量仅为粒径120 nm的55.9%~70.3%。结果表明,亲水性且表面电荷接近中性、大小适宜的mPEG-PLGA-NPs对黏蛋白具有一定的黏惰性,能够快速穿透HGC-27细胞周围黏液被细胞摄取。mPEG-PLGA-NPs有望成为一种新型的载药系统用于胃黏液癌的治疗。     

RGD肽修饰紫杉醇聚合物纳米粒的制备及其药效学研究

制备靶向肽c(RGDyK)修饰的紫杉醇聚合物纳米粒,并对其体内外药效学性质进行评价。采用透析法制备靶向肽修饰的包载紫杉醇(PTX)的低相对分子质量肝素-全反式维甲酸聚合物(PTX-LHRyK)纳米粒,测定其粒度分布、Zeta电位、载药量和包封率等理化性质,通过体外细胞毒实验和体内药效学实验评价PTX-LHRyK纳米粒的抗肿瘤效果。制得的PTX-LHRyK纳米粒的粒径为(131.7±2.3)nm,Zeta电位为(-27.1±2.3)mV,载药量和包封率分别为(32.03±0.11)%和(84.84±2.63)%。随着孵育时间的延长,PTX-LHRyK纳米粒对B16F10细胞的毒性增加,孵育72 h后对B16F10细胞的IC₅₀为(41.6±7.2)ng/mL,LHRyK载体对B16F10细胞的存活率无显著影响。体内药效学研究显示,PTX-LHRyK纳米粒的抑瘤率达到75.28%,是混合药物溶液组的1.46倍,纳米粒制剂组的小鼠体重和相对脾重均无显著性变化。因此,PTX-LHRyK纳米粒粒径小,载药量高,可明显提高紫杉醇的抗肿瘤治疗效果,且降低药物的不良反应。     

基于哈贝仿生复合纳米材料固定酶的过氧化氢生物传感器

目的：构建基于纳米金-聚多巴胺-氧化石墨烯-甲苯胺蓝（A PG T ）哈贝仿生复合纳米材料制备的H2 O2生物传感器,并研究该传感器的性能。方法采用一步原位聚合法制备APGT ,并采用紫外-可见光谱、扫描电镜、X射线能谱及电化学方法对该传感器进行表征。结果该电化学传感器表现出对 H2 O2良好的电催化还原行为,线性范围为1．0～40．0μmol/L ,检测限为0．32μmol/L ,表观米氏常数为16．9μmol/L。结论该生物传感器制备简单、绿色,具有较高的稳定性,较低的检出限和较小的米氏常数,且具有重现性好和抗干扰能力强等特点。     

Hemocompatibility and biocompatibility of antibacterial biomimetic hybrid films

In previous work, we developed novel antibacterial hybrid coatings based on dextran containing dispersed Ag NPs (~ 5 nm, DEX-Ag) aimed to offer dual protection against two of the most common complications associated with implant surgery, infections and rejection of the implant. However, their blood-material interactions are unknown. In this study, we assess the hemocompatibility and biocompatibility of DEX-Ag using fresh blood and two cell lines of the immune system, monocytes (THP-1 cells) and macrophages (PMA-stimulated THP-1 cells). Glass, polyurethane (PU) and bare dextran (DEX) were used as reference surfaces. PU, DEX and DEX-Ag exhibited non-hemolytic properties. Relative to glass (100%), platelet attachment on PU, DEX and DEX-Ag was 15%, 10% and 34%, respectively. Further, we assessed cell morphology and viability, pro-inflammatory cytokines expression (TNF-α and IL-1β), pro-inflammatory eicosanoid expression (Prostaglandin E₂, PGE₂) and release of reactive oxygen species (ROS, superoxide and H₂O₂) following incubation of the cells with the surfaces. The morphology and cell viability of THP-1 cells were not affected by DEX-Ag whereas DEX-Ag minimized spreading of PMA-stimulated THP-1 cells and caused a reduction in cell viability (16% relative to other surfaces). Although DEX-Ag slightly enhanced release of ROS, the expression of pro-inflammatory cytokines remained minimal with similar levels of PGE₂, as compared to the other surfaces studied. These results highlight low toxicity of DEX-Ag and hold promise for future applications in vivo.     

壳聚糖修饰雷公藤多苷纳米粒的制备及其体外释药研究

目的 制备壳聚糖修饰雷公藤多苷纳米粒（LMWC-TG-NPs）,并研究其体外释药行为。方法 采用改良的自乳化溶剂扩散法制备LMWC-TG-NPs;正交试验设计优化雷公藤多苷纳米粒（TG-NPs）处方,单因素试验考察壳聚糖（LMWC）修饰方式;以含20%乙醇的PBS（pH 7.4）为释放介质考察LMWC-TG-NPs的体外释药行为。结果 优化的处方工艺：以1.0% Poloxamer 188、80 mg PLA、12 mL有机相、丙酮-乙醇（2∶3）制备TG-NPs混悬液,以与TG-NPs混悬液等体积的10% LMWC溶液修饰TG-NPs制备LMWC-TG-NPs;根据优化条件制备的LMWC-TG-NPs,外观呈圆形或类圆形,平均粒径为（207.6±3.4）nm,多分散指数（PDI）为0.078±0.009（n＝3）,包封率和载药量分别为（61.83±2.43）%、（10.70±0.37）%（n＝3）;体外释药符合Higuchi方程。结论 所制备的LMWC-TG-NPs包封率较高,粒径小,体外释药具有明显的缓释特征,为后期研究其肾脏靶向和毒性奠定了基础。     

冬凌草甲素长循环固体脂质纳米粒的制备及对人胃癌SGC-7901细胞的抑制作用

目的制备冬凌草甲素长循环固体脂质纳米粒（ORI-LSLN）,并考察其理化性质和对人胃癌SGC-7901细胞的抑制作用。方法采用熔融均质法制备ORI-LSLN,并对其形态、粒径分布、电位、包封率和载药量等性质进行考察。以冬凌草甲素溶液（ORI）、冬凌草甲素固体脂质纳米粒（ORI-SLN）为对照,进行ORI-LSLN体外释放试验。采用MTT法测定ORI-LSLN对人胃癌SGC-7901细胞的抑制作用。结果制备的ORI-LSLN呈类球形,平均粒径112 nm,Zeta电位为-31.6 mV,包封率为90.4%,载药量为5.1%。体外释放结果表明,ORI-SLN和ORI-LSLN在释放初期并无显著区别,后期ORI-SLN释放较快,24 h基本释放完全,而ORI-SLN则需要36 h才完全释放,表现了更好的缓释效果。ORI-LSLN对人胃癌SGC-7901细胞具有较强的毒性作用。结论熔融均质法制备的ORI-LSLN包封率高、载药量大,工艺易于工业化,与ORI-SLN相比,ORI-LSLN更具有较好的抗癌药物缓释制剂潜力。     

完整结肠系膜切除在进展期结肠癌的应用研究

目的 探讨完整结肠系膜切除（complete mesocolic excision,CME）在进展期结肠癌患者手术治疗的应用价值.方法 总结分析我院胃肠外科本手术治疗小组2011年1月~2012年12月期间确诊为结肠癌II~III期患者行CME手术治疗（CME组43例）的临床资料,回顾性对比同一手术组2009年1月~2010年12月期间确诊为结肠癌II期至III期患者行传统根治术（对照组46例）的临床资料,对比两组手术效果.结果 CME组与对照组比较,II期患者淋巴结清扫数目差异无统计学意义（P〉0.05）;III期患者淋巴结清扫数目及阳性淋巴结数目差异均有统计学意义（P〈0.01）;平均手术时间,术后排气、排便时间差异均无统计学意义（P〉0.05）;术中出血量差异有统计学意义（P〈0.01）.结论 进展期结肠癌采用CME方法,符合肿瘤操作原则及现代外科精细操作的要求,不增加平均手术时间、手术风险及并发症的发生率,显著提高III期患者的根治效果.