表没食子儿茶素没食子酸酯纳米颗粒的制备及其体外抗白血病效应研究

目的：制备表没食子儿茶素没食子酸酯（EGCG）-壳聚糖（CS）纳米颗粒，并比较EGCG纳米颗粒与原料药对人急性淋巴细胞白血病细胞系Jurkat细胞的抑制作用。方法：选取壳聚糖（CS）为包封材料，采用注入-超声法将EGCG装载到CS形成的纳米粒中，制备出EGCG纳米颗粒。使用激光粒度仪对纳米EGCG的粒径和Zeta电位进行测定，采用场发射扫描电子显微镜观察其形态结构。采用CCK-8实验检测EGCG纳米颗粒抑制Jurkat细胞增殖的作用，采用流式细胞术检测其对Jurkat细胞凋亡的影响，比较EGCG纳米颗粒与原料药的体外抗白血病效应。结果：最优条件下制备的EGCG纳米颗粒包封率为（76±4）%，平均粒径为（116±25）nm，平均Zeta电位为（61.2±1.8）mV，具有球形微观结构。EGCG纳米颗粒抑制Jurkat细胞增殖作用及促Jurkat细胞凋亡作用显著高于EGCG原料药。结论：EGCG纳米颗粒在体外抗白血病效应明显优于原料药，为进一步探索其体内抗白血病效应提供了依据。     

单分散性介孔二氧化硅的制备及靶向性评价

目的：为了制备可稳定分散的介孔二氧化硅纳米材料，并将其用于尾静脉注射的纳米制剂。方法：本文采用Stober法，以十六烷基三甲基溴化铵（CTAB）为模板剂，正硅酸乙酯（TEOS）为硅源，通过酸液萃取法去除模板，制备出分散性良好的MSN纳米粒。通过FTIR、扫描电子显微镜及透射电镜等仪器，进行结构和形貌的表征。结果：单因素实验结果可知MSN的最佳制备工艺为：CTAB/TEOS质量比为1：5，pH 10，反应温度70~80℃，搅拌速率为500 r·min^-1。MSN负载DOX，表现出高负载率；体外释放实验表明DOX在中性条件下释放缓慢，弱酸性条件下释放迅速；体内实验表明MSN具有良好的靶向性。结论：通过优化后的制备工艺，MSN可稳定分散，该制剂制备方法简单，具有pH敏感性，良好的靶向性，有利于达到肿瘤靶向给药的要求，介孔二氧化硅在靶向传递系统的应用具有广阔前景。     

新型氨基酸修饰羟基磷灰石纳米复合缓释材料的制备与释药特性研究

目的：本文设计并合成了新型聚氨基酸纳米羟基磷灰石缓释材料,并以替莫唑胺为模型药物,对所合成材料的体外释药性能进行研究。方法：采用微乳液法制备多孔羟基磷灰石,以天冬氨酸单体为原料,合成聚氨基酸高分子材料,利用高分子化合物水溶液中的蜷缩成膜性能与羟基磷灰石组成复合缓释纳米材料。以替莫唑胺为模型药物,对所制备的复合纳米缓释制剂的体外释放性能进行研究。结果：所制备的替莫唑胺-纳米复合羟基磷灰石缓释制剂为光滑的纳米球制剂,体外释放实验显示,可起到长约200 h的缓释效果。结论：本文制备的替莫唑胺复合纳米羟基磷灰石缓释制剂具有长期的缓释性能,可潜在适用于体内植入给药。     

载血卟啉单甲醚中空金纳米球的光热光动力联合抗肿瘤研究

目的 设计基于中空金纳米球的新型纳米给药系统(HMME-PEI-HAuNS),在近红外光照射下研究其同步光热光动力联合抗肿瘤作用。方法 以钴纳米粒为模板制备中空金纳米球(HAuNS),将血卟啉单甲醚(HMME)通过枝状聚乙烯亚胺(PEI)装载到HAuNS表面,形成纳米给药系统(HMME-PEI-HAuNS);采用核磁共振氢谱、红外光谱、紫外光谱分析对HMME-PEI-HAuNS进行结构确证。建立荷瘤(SKOV3)小鼠模型,通过荧光活体成像仪考察其体内分布情况。将对肿瘤细胞表面EphB4受体具有特异性亲和力的靶向多肽TNYL修饰于其表面以增强该纳米体系的靶向性,用核染试剂Hoechst染色SKOV3细胞,在激光共聚焦显微镜下观察细胞内的荧光强度,用MTT比色法进行细胞毒性评价。结果 HAuNS能对HMME进行成功装载,装载率达63.4±5.2%。由于肿瘤的高通透性和滞留效应(EPR 效应),HMME-PEI-HAuNS较游离HMME和HMME-PEI胶束在肿瘤部位有更多的累积量和更长的滞留时间,累计效率约为1.6%。荧光定量统计显示在TNYL多肽的介导下纳米球的靶向性更高,在808 nm激光照射下,TNYL-HMME-PEI-HAuNS发挥光热和光动力协同作用产生强大的肿瘤杀伤作用,在高浓度时,细胞存活率不到10%。结论 主动靶向纳米球(TNYL-HMME-PEI-HAuNS)在808 nm近红外光照射下具有较强的光热光动力联合抗肿瘤作用。     

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.     

纳米金在肿瘤诊断治疗中的研究现状

纳米金基于自身易于制备,形貌及尺寸可控,低细胞毒性,稳定性好,温和的表面化学性质以及良好的生物相容性,独特的SPR(表面等离子共振效应)和光散射等物理特性,加上其容易被多种基团修饰后获得对肿瘤细胞的靶向性,使其在肿瘤治疗、成像等方面受到越来越广泛的关注,逐渐成为当前抗肿瘤研究的热点。该文就纳米金的特点以及纳米金在肿瘤的诊断、治疗中的研究现状进行综述。     

大内径多壁碳纳米管基靶向缓释载药系统的制备及性能

目的制备大内径多壁碳纳米管（LID-MWCNT）基靶向抗肿瘤药物缓释系统,分析其功能特性并检测其对肿瘤细胞的增殖抑制作用。方法纯化、切割LID-MWCNT,制备碳管载体及同源封堵物超短LID-MWCNT （UST）。碳管表面负载靶向分子叶酸（FA）及荧光标记分子;管内负载抗肿瘤药物顺铂（CDDP）,并以UST 封堵药物通道。观察载药系统显微形态;测定载药率及药物释放曲线;观察载药系统对肿瘤细胞的靶向趋化状况及增殖抑制效应。结果成功制备大内径多壁碳纳米管基靶向抗肿瘤药物缓释系统（CDDP@UST-FA-LID-MWCNT）,其载药率为70.97%。体外释放呈双相缓释模式,持续释放时间约18 h。载体系统具备了一定靶向趋化能力;较低载药浓度的 CDDP@UST-FA-LID-MWCNT 即对肿瘤细胞具有增殖抑制作用,且随着药物浓度的增加,抑制作用增强。结论载药系统CDDP@UST-FA-LID-MWCNT 具有较高的载药率及良好的药物缓释效果,能够靶向作用于肿瘤细胞,具有较强的抗肿瘤作用。     

铁基纳米材料用于肿瘤免疫调节的研究进展

随着纳米医学、生物医学、材料学等学科的融合发展,铁基纳米材料在肿瘤免疫调节和联合抗肿瘤治疗领域正在吸引研究者的目光。铁基纳米材料可触发肿瘤细胞铁死亡,诱导免疫原性细胞死亡,激活肿瘤免疫微环境,作为肿瘤疫苗载体等,具备联合化疗、免疫治疗等提高抗肿瘤综合效能的潜力和可行性。此外,铁基纳米材料可作为核磁共振成像（MRI）造影剂用于肿瘤诊断,其磁靶向性、磁热性等特性使其在靶向热疗方面同样具有较大的潜力。近年来仿生化的设计赋予铁基纳米材料更优的肿瘤靶向性、体内免疫清除豁免、肿瘤免疫调节等功能。该文对铁基纳米材料在肿瘤治疗及应用的进展进行分类综述,并提出了目前面临的挑战以及可能的解决方案。     

合成纳米材料可用于靶向递送抗肿瘤药物

许多癌症的治疗都朋到了综合治疗法——也就是将多个特定诊断有针对性的检测和治疗结合起来：Sailor等目前报道 了一项纳米系统,它由2种截然不同的合成纳米材料组成,这些材料可以携手合作发掘病变组织,并将药物输送至肿瘤部位,其作用比单个纳米颗粒治疗方法更加见效。     

秋水仙碱纳米控释微粒抗肿瘤的实验研究

目的：研究不溶于水的植物性抗癌药秋水仙碱纳米控释静脉注射微粒的制备工艺及其体内外抗肿瘤作用。方法：以聚乳酸－聚乙醇酸共聚物（PLGA）作为基质材料,采用超声乳化－溶剂挥发法制备PLGA包载秋水仙碱的纳米级微粒（NP）。借助扫描电镜观察PLGA－秋水仙碱－NP微粒形态,通过激光光散射实验测定纳米微粒的粒径分布。利用高效液相色谱（HPLC）测定纳米微粒制剂的载药率,以MTT方法做体外杀伤癌细胞实验,进行不同剂量,给药频度条件下体内抑瘤实验。结果：经电镜观察PLGA－秋水仙碱－NP为表现光滑的球形微粒,粒径分布平均值是104．9nm,呈正态分布,PLGA－秋水仙碱－NP载药率为33．0％。体外MTT实验提示纳米粒子粒子与裸药作用相同且显著控释,体内抑制实验表明：控释制剂间隔给药疗效优于包载药物每日给药的疗效,量－效关系, 毒性显著减低,经静脉途径试用无任何不良反应。结论：PLGA纳米粒子可以作为抗肿瘤药物秋水仙碱的有效载体,并可在不添加助溶剂等前提下成功制备其静脉注射剂型,实现药物控制释放并减低毒性,发挥药物更佳的抗肿瘤作用。     

Near-infrared light-activated IR780-loaded liposomes for anti-tumor angiogenesis and Photothermal therapy

Tumor angiogenesis is a key step in the process of tumor development, and antitumor angiogenesis has a profound influence on tumor growth. Herein we report a dual-function drug delivery system comprising a Near-infrared (NIR) dye and an anti-angiogenic drug within liposomes (Lip-IR780-Sunitinib) for enhanced antitumor therapy. The hydrophobic NIR dye IR780 was loaded into the liposome phospholipid bilayer, and the bilayer would be disrupted by laser irradiation so that anti-angiogenic drug sunitinib release would be activated remotely at the tumor site. The released hydrophilic sunitinib could potentially target multiple VEGF receptors on the tumor endothelial cell surface to inhibit angiogenesis. Meanwhile, IR780-loaded liposomes kill the cancer cells by photothermal therapy. Lip-IR780-Sunitinib exhibited enhanced anti-tumor and anti-angiogenic effects in vitro and in vivo. This system facilitates easy and controlled release of cargos to achieve anti-tumor angiogenesis and photothermal therapy.     

Trimodal synergistic antitumor drug delivery system based on graphene oxide

A multifunctional antitumor drug delivery system was synthesized based on graphene oxide (GO) for near-infrared (NIR) light controlling chemotherapeutic/photothermal (PTT) /photodynamic (PDT) trimodal synergistic therapy. The system named ICG-Wed-GO was formed by co-loading wedelolactone (Wed) and indocyanine green (ICG) on the surface of GO through π–π stacking interaction. Under NIR laser irradiation, ICG-Wed-GO could effectively absorb and transform optical energy to heat, generate reactive oxygen species (ROS) to ablating and damage tumor cells. The temperature of ICG-Wed-GO solution reached up to 79.4?°C in 10?min with NIR irradiation. In in vitro and in vivo study, ICG-Wed-GO showed excellent antitumor effect. After 14-day treatment of ICG-Wed-GO with NIR laser irradiation, the tumor disappeared completely on tumor-bearing mice. The low biotoxicity of ICG-Wed-GO was also proved. The system achieved the synergistic trimodal chemotherapeutic/photothermal/photodynamic treatment and demonstrated excellent antitumor effect, which is expected to have a greater potential for cancer therapy.     

Folic acid-modified and functionalized CuS nanocrystal-based nanoparticles for combined tumor chemo- and photothermal therapy

Recent studies have identified that CuS nanocrystal (CuS NCs) could be used as a new class of promising photo-thermal agents due to their excellent plasmonic absorption abilities in a wide near-infrared (NIR) region. However, most of nanocarriers lack target capacity for combining chemotherapy and photothermal therapy effects. Herein, we reported chitosan (CS)-encapsulated and folic acid (FA)-modified nanoparticles (NPs) simultaneously loading with functionalized CuS NCs and docetaxel (DTX) (FA-DTX-PVP/CuS-NPs). Compared with free DTX, the photothermal agent CuS NCs and DTX not only could be specially targeted to deliver into MCF-7 cancer cells via a receptor-mediated endocytosis pathway, but also could be effectively transferred into tumor tissues of S₁₈₀ tumor-bearing mice in vivo. More important, when combination with NIR laser irradiation, FA-DTX-PVP/CuS-NPs showed a higher antitumor efficacy than the individual therapies. Thus, as a remote and noninvasive tumor therapy strategy, these active targeting NPs may provide a great potential for tumor synergistic therapy.     

Near-Infrared Light-Sensitive Liposomes for the Enhanced Photothermal Tumor Treatment by the Combination with Chemotherapy

Purpose

To develop a near-infrared (NIR) light-sensitive liposome, which contains hollow gold nanospheres (HAuNS) and doxorubicin (DOX), and evaluate their potential utility for enhancing antitumor activity and controlling drug release.

Methods

The liposomes (DOX&HAuNS-TSL) were designed based on a thermal sensitive liposome (TSL) formulation, and hydrophobically modified HAuNS were attached onto the membrane of the liposomes. The behavior of DOX release from the liposomes was investigated by the dialysis, diffusion in agarose gel and cellular uptake of the drug. The biodistribution of DOX&HAuNS-TSL was assessed by i.v. injection in tumor-bearing nude mice. Antitumor efficacy was evaluated both histologically using excised tissue and intuitively by measuring the tumor size and weight.

Results

Rapid and repetitive DOX release from the liposomes (DOX&HAuNS-TSL), could be readily achieved upon NIR laser irradiation. The treatment of tumor cells with DOX&HAuNS-TSL followed by NIR laser irradiation showed significantly greater cytotoxicity than the treatment with DOX&HAuNS-TSL alone, DOX-TSL alone (chemotherapy alone) and HAuNS-TSL plus NIR laser irradiation (Photothermal ablation, PTA, alone). In vivo antitumor study indicated that the combination of simultaneous photothermal and chemotherapeutic effect mediated by DOX&HAuNS-TSL plus NIR laser presented a significantly higher antitumor efficacy than the PTA alone mediated by HAuNS-TSL plus NIR laser irradiation.

Conclusions

Our study could be as the valuable reference and direction for the clinical application of PTA in tumor therapy.     

Indocyanine green-containing nanostructure as near infrared dual-functional targeting probes for optical imaging and photothermal therapy

Indocyanine green (ICG) is a near-infrared (NIR) imaging agent and is also an ideal light absorber for laser-mediated photothermal therapy. This NIR dye could serve as a basis of a dual-functional probe with integrated optical imaging and photothermal therapy capabilities. However, applications of ICG remain limited by its concentration-dependent aggregation, poor aqueous stability, nonspecific binding to proteins and lack of target specificity. To overcome these limitations, a novel ICG-containing nanostructure is designed utilizing the noncovalent self-assembly chemistry between phospholipid-polyethylene glycol (PL-PEG) and ICG. The interactions between both amphiphilic ICG and PL-PEG were studied using absorption and fluorescence spectroscopy. The properties of ICG-PL-PEG nanoprobe, such as absorption and fluorescence spectra, stability, morphology and size distribution, were also investigated. Two representative targeting molecules, namely, a small molecule, folic acid (FA), and a large protein, integrin α(v)β? monoclonal antibody (mAb), were conjugated to the surface of ICG-PL-PEG nanoprobe, displaying the diversity of ligand conjugation. The target specificity was confirmed using three cell lines with different levels of available folate receptors (FRs) or integrin α(v)β? expression via laser scanning confocal microscope and flow cytometry. This targeting ICG-PL-PEG nanoprobe could be internalized into targeted cells via ligand-receptor mediated endocytosis pathway. Our in vitro experiments showed that internalized ICG-PL-PEG could be used for cell imaging and selective photothermal cell destruction. These results represent the first demonstration of the dual functionality of ICG-containing nanostructure for targeted optical imaging and photothermal therapy of cancerous cells. This novel ICG-PL-PEG nanostructure, when conjugated with other therapeutic and imaging agents, could become a multifunctional probe for cancer diagnosis and treatment.     

Magnetic nanoparticles modified-porous scaffolds for bone regeneration and photothermal therapy against tumors

For effectively treating tumor related-bone defects, design and fabrication of multifunctional biomaterials still remain a great challenge. Herein, we firstly fabricated magnetic SrFe₁₂O₁₉ nanoparticles modified-mesoporous bioglass (BG)/chitosan (CS) porous scaffold (MBCS) with excellent bone regeneration and antitumor function. The as-produced magnetic field from MBCS promoted the expression levels of osteogenic-related genes (OCN, COL1, Runx2 and ALP) and the new bone regeneration by activated BMP-2/Smad/Runx2 pathway. Moreover, the SrFe₁₂O₁₉ nanoparticles in MBCS improved the photothermal conversion property. Under the irradiation of near-infrared (NIR) laser, the elevated temperatures of tumors co-cultured with MBCS triggered tumor apoptosis and ablation. As compared with the pure scaffold group, MBCS/NIR group possessed the excellent antitumor efficacy against osteosarcoma via the hyperthermia ablation. Therefore, the multifunctional MBCS with excellent bone regeneration and photothermal therapy functions has a great application for treating the tumor-related bone defects.     

Enhancing of plasmonic photothermal therapy through heat-inducible transgene activity

We explore the synergistic effect of photothermal therapy and gene therapy, simultaneously triggered by silica-gold nanoshells (NS) or hollow gold nanoparticles (HGNPs) in human HeLa cells following near-infrared (NIR) light irradiation. Thermal transfer from NS was higher than that displayed by HGNPs, owing to a differential interaction of the nanomaterial with the biological environment. Under sublethal photothermal conditions, NS and HGNPs effectively modulated the expression levels of a DsRed-monomer reporter gene controlled by the highly heat-inducible human HSP70B promoter, as a function of nanomaterial concentration and length of laser exposure. Hyperthermia treatments at doses that do not promote cell death generated a lethal outcome in HeLa cells harboring the fusogenic GALV-FMG transgene under the control of the HSP70B promoter. Combination of lethal photothermia with the triggering of the cytotoxic transgene resulted in a dramatic increase of the cell-ablation area as a result of the synergistic activity established.From the Clinical EditorIn this study photothermal therapy and gene therapy, simultaneously triggered by silica-gold nanoshells or hollow gold nanoparticles, was investigated in human HeLa cells following near-infrared (NIR) light irradiation. It is shown that the combination of lethal photothermia with the triggering of the cytotoxic transgene at sublethal levels results in a synergistic cytotoxic effect in vitro.     

In-vivo cancer cell destruction using porous silicon nanoparticles

In-vivo animal tests were performed to investigate the feasibility of photothermal therapy based on porous silicon nanoparticles (PSiNPs) in combination with a near-infrared (NIR) laser. The in-vivo animal test results showed that the murine colon carcinoma (CT-26) tumors were completely resorbed with minimal damage to surrounding healthy tissue within 5 days after PSiNPs and NIR laser treatments. In contrast, tumors in the groups treated only with PSiNPs or NIR and a control group continued to grow until the mice died. All of the mice treated with both PSiNPs and NIR remained healthy and free of tumors even 90 days after the treatment. In-vivo fluorescence imaging and the urine and feces tests revealed that PSiNPs injected intratumorally into mice were cleared mainly through the urine. The in-vivo animal test results suggest that thermotherapy based on porous silicon in combination with NIR laser irradiation can efficiently destroy cancer cells selectively without damaging the surrounding healthy cells.     

Morphological study on apoptosis Hela cells induced by soyasaponins.

Soyasaponins are present in legumes and soybeans are the primary dietary source of saponins. SS-II, the second fraction of soyasaponins, was separated by column chromatographic method with D101A macroporous resin from soybean. In this paper, at the concentration range of 100-400 mg/L, SS-II had obvious cytotoxic effect on Hela cells by MTT assay. After Hela cells were treated with SS-II, typical apoptotic morphological changes, including nuclear fragmentation, cytoplasm shrinkage and decrease of cell volume, were observed by fluorescence microscope, transmission electron microscope (TEM) and confocal laser scanning microscope (CLSM), respectively. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay also confirmed that SS-II-treated Hela cells showed apoptotic features. The results suggested that soyasaponins were a potential antitumor compound and the apoptosis induced by soyasaponins was a key antitumor mechanism.