纳米金在分子影像学中的应用进展

分子影像学的出现将传统的以解剖结构为成像基础的医学影像学带入到以图像阐释细胞／分子结构和功能以及病理改变的新时代。伴随着“后基因组”时代的到来以及“个体化医疗”的兴起,分子影像学对医学领域带来了里程碑式的革命并日益发挥重要作用。在分子影像领域,寻找最佳的分子影像探针／对比剂以及成像方法,以获取更多的细胞或者分子的功能及病理改变的信息日益成为热门的研究领域。纳米金籍其自身的优点在分子影像学的发展中展示出日益广阔的前景。本文就分子影像学的相关技术及纳米金在分子影像学中的应用进展作一简要综述。     

纳米递送系统线粒体靶向策略在肿瘤诊疗中的应用

肿瘤是危害人类健康的重大疾病之一。目前用于肿瘤治疗的方法有手术治疗、化学药物治疗、放射治疗等。然而,传统的治疗方法存在治疗效果不佳、易引发多药耐药、毒副作用大等缺点,仍需进一步探索新的肿瘤治疗靶点和策略。线粒体作为细胞的能量转换器,被认为是肿瘤、心血管和神经性疾病新药设计的最重要靶点之一。纳米药物递送载体具有易被主动靶向基团修饰的特点,可实现细胞乃至细胞器的精准靶向给药。本文从抑制肿瘤细胞增殖、促进肿瘤细胞凋亡、抑制肿瘤复发与转移、诱导细胞自噬等方面综述了线粒体靶向纳米载体在肿瘤诊疗中的应用。     

纳米金在分子影像学中的应用进展

分子影像学的出现将传统的以解剖结构为成像基础的医学影像学带入到以图像阐释细胞/分子结构和功能以及病理改变的新时代。伴随着"后基因组"时代的到来以及"个体化医疗"的兴起,分子影像学对医学领域带来了里程碑式的革命并日益发挥重要作用。在分子影像领域,寻找最佳的分子影像探针/对比剂以及成像方法,以获取更多的细胞或者分子的功能及病理改变的信息日益成为热门的研究领域。纳米金籍其自身的优点在分子影像学的发展中展示出日益广阔的前景。本文就分子影像学的相关技术及纳米金在分子影像学中的应用进展作一简要综述。     

纳米金在肿瘤成像和放射治疗领域的应用进展

纳米金颗粒以其优越的理化性质在医学领域发挥独特的作用.近年来越来越多的研究证实了纳米金在肿瘤早期诊断和治疗方面方面有重要作用,尤其是纳米金正被逐步应用肿瘤成像和治疗领域.本文从纳米金的性质,在肿瘤成像和放射治疗方面的应用进展等方面作一综述.     

纳米金在基因突变检测及SNP分析中的应用

对特异核苷酸序列的高选择性检测在生物医学研究和临床检测中日趋重要. 纳米金特殊的光学性质、电学性质、化学性质、以及良好的生物相容性,使之成为检测生物大分子的首选工具.本文介绍了几种典型的基因突变检测及单核苷酸多态性(SNP)分析系统：基因芯片、生物传感器和光学检测系统.综述了多种颇有新意的检测方法和原理,详细阐明了它们的检测机制和研究进展,分析并比较了纳米金不同的作用方式,为纳米金在突变检测上的进一步研究提供了一定思路和参考.     

纳米粒子在肝癌靶向治疗中的应用研究进展

增强抗癌药物对癌细胞的选择性、降低其毒副作用及提高疗效一直是肝癌治疗领域一项重要的研究课题,纳米药物载体的研究有望解决这些问题。目前纳米粒子在肝癌靶向治疗中的应用研究集中于被动靶向治疗、主动靶向治疗、基因治疗、栓塞化疗及纳米粒子的直接治疗作用等方面。     

纳米疫苗在肿瘤免疫疗法中的应用

近年来肿瘤免疫疗法成为癌症治疗领域的热点,其中结合肿瘤疫苗和纳米技术的纳米疫苗为肿瘤免疫疗法提供了新思路.纳米疫苗可以实现疫苗和佐剂的共载,且智能化的纳米载体进一步实现了抗原有效的靶向递送,促进了抗原的摄取和递呈,激活抗原特异性免疫应答,有效杀伤肿瘤细胞.本文就纳米疫苗的原理、优势、纳米材料的类型、临床疗效进行综述,为后期纳米疫苗的设计提供更可靠的参考依据.     

盐霉素抗肿瘤作用研究进展

盐霉素(salinomycin)特异性杀伤肿瘤干细胞(cancer stem cell,CSC)作用的发现,引起了国内外学者的广泛关注.最近的研究表明,盐霉素能高选择性杀死小鼠身上的人乳腺癌CSC并且其效力比紫杉醇高100倍.盐霉素这种靶向作用于CSC的能力及较好的成药性,使其具有研发为一种新型的抗癌药物的潜能.通过手术及术后化疗抗癌的传统方法已经难以对抗肿瘤的复发或转移.然而,利用离子型载体抗生素即盐霉素杀伤肿瘤干细胞这一特性,消除肿瘤复发与转移的”根源”,从而达到治愈”癌症”这一顽疾的目的在理论上是可行的.多项研究已证实盐霉素能对抗多种肿瘤干细胞,因此我们认为盐霉素是一种广谱抗肿瘤药物,这些结论将推动临床抗肿瘤研究进入一个崭新的阶段,为防癌治癌工作提供实验依据和新的思路.本文将系统阐述盐霉素抗肿瘤药效学及其作用机制的研究进展,以期为后续临床研发抗癌新化合物提供参考.     

重组抗体工程及其在肿瘤靶向及癌症治疗中的应用

在过去的十几年中,重组抗体工程在基础研究、医学和药物生产上已经成为最有希望的领域之一。重组抗体及其片段在正在进行诊断和治疗的临床试验中占所有生物蛋白的30％以上。研究集中在抗体作为理想的癌症靶向试剂方面,最近由于FDA批准使用第一个工程化治疗抗体而使热度达到极点。过去的几年中,在设计、筛选及生产新型工程化抗体方面已经取得了重大进展。改革的筛选方法已经能够分离出高亲和力的癌－靶向及抗病毒的抗体,后能够抑制病毒用于基因治疗。癌症诊断和治疗的另一个策略是将重组抗体片段与放射性同位素、药物、毒素、酶以及生物传感器表面进行融合。双特异性抗体及相关融合蛋白也已经生产出来用于癌症的免疫治疗,在抗癌疫苗以及T细胞补充策略上有效地增强了人免疫应答。     

纳米级金微粒在DNA生物传感器研究中的应用

纳米金颗粒具有独特的物理、化学性质和良好的生物兼容性,已广泛应用于生命科学研究中的示踪技术.将该技术与DNA传感器相结合,可显著提高生物传感器的灵敏度,缩短检测时间和提高检测通量,已成为近年来的研究重点.     

Application of phototherapeutic-based nanoparticles in colorectal cancer

Colorectal cancer (CRC) is the third most commonly diagnosed malignancy and the second leading cause of cancer death, which accounts for approximately 10% of all new cancer cases worldwide. Surgery is the main method for treatment of early-stage CRC. However, it is not effective for most metastatic tumors, and new treatment and diagnosis strategies need to be developed. Photosensitizers (PSs) play an important role in the treatment of CRC. Phototherapy also has a broad prospect in the treatment of CRC because of its low invasiveness and low toxicity. However, most PSs are associated with limitations including poor solubility, poor selectivity and high toxicity. The application of nanomaterials in PSs has added many advantages, including increased solubility, bioavailability, targeting, stability and low toxicity. In this review, based on phototherapy, we discuss the characteristics and development progress of PSs, the targeting of PSs at organ, cell and molecular levels, and the current methods of optimizing PSs, especially the application of nanoparticles as carriers in CRC. We introduce the photosensitizer (PS) targeting process in photodynamic therapy (PDT), the damage mechanism of PDT, and the application of classic PS in CRC. The action process and damage mechanism of photothermal therapy (PTT) and the types of ablation agents. In addition, we present the imaging examination and the application of PDT / PTT in tumor, including (fluorescence imaging, photoacoustic imaging, nuclear magnetic resonance imaging, nuclear imaging) to provide the basis for the early diagnosis of CRC. Notably, single phototherapy has several limitations in vivo, especially for deep tumors. Here, we discuss the advantages of the combination therapy of PDT and PTT compared with the single therapy. At the same time, this review summarizes the clinical application of PS in CRC. Although a variety of nanomaterials are in the research and development stage, few of them are actually on the market, they will show great advantages in the treatment of CRC in the near future.     

Nanovectors for anticancer agents based on superparamagnetic iron oxide nanoparticles

During the last decade, the application of nanotechnologies for anticancer drug delivery has been extensively explored, hoping to improve the efficacy and to reduce side effects of chemotherapy. The present review is dedicated to a certain kind of anticancer drug nanovectors developed to target tumors with the help of an external magnetic field. More particularly, this work treats anticancer drug nanoformulations based on superparamagnetic iron oxide nanoparticles coated with biocompatible polymers. The major purpose is to focus on the specific requirements and technological difficulties related to controlled delivery of antitumoral agents. We attempt to state the problem and its possible perspectives by considering the three major constituents of the magnetic therapeutic vectors: iron oxide nanoparticles, polymeric coating and anticancer drug.     

Unveiling the anticancer and antimycobacterial potentials of bioengineered gold nanoparticles

Synthesis of gold nanoparticles was carried out using Pongammia pinnata (pongam) leaf extract and their anticancer and antimycobacterial activities were studied. Gold nanoparticle formation was confirmed by UV–vis, XRD and HR-TEM. The anticancer efficacies of the biogenic gold nanoparticles were analyzed using cytotoxicity, cell morphology analysis, oxidative DNA damage, apoptosis detection and toxicity studies. Biogenic gold nanoparticles inhibited breast cancer cell line (MCF-7) proliferation with an efficacy of IC₅₀ of 1.85 μg/mL. The antimycobacterial potential of the biogenic gold nanoparticles was screened against M. tuberculosis by Luciferase Reporter Phage (LRP) assay. The gold nanoparticles showed inhibition against sensitive M. tuberculosis with the minimum inhibitory concentration (MIC) of 10 μg/mL whereas no inhibition was found against the rifampicin resistant M. tuberculosis.     

透明质酸在肿瘤治疗中的应用

透明质酸(hyaluronic acid,HA)是脊椎动物细胞间基质的重要组成成分,它是一种线性生物多聚糖,具有良好的生物相容性、生物可降解、无毒、无免疫原性等特点,在生物医药领域有广泛的应用。本文简要介绍透明质酸的结构特点及其靶向作用机制,综述近年来透明质酸作为药物载体和靶向因子在肿瘤治疗中的研究现状。     

靶向抑制VEGF在肺癌治疗中的应用前景

血管内皮生长因子（vascular endothelial growth factor,VEGF）是介导肿瘤血管生成最重要因子,与肺癌细胞增殖、转移及预后密切相关。靶向沉默VEGF基因及抑制其受体表达在肺癌治疗中具有光明的应用前景。本文就此进行综述。     

Circulation and distribution of gold nanoparticles and induced alterations of tissue morphology at intravenous particle delivery

Kinetics, biodistribution, and histological studies were performed to evaluate the particle‐size effects on the distribution of 15 nm and 50 nm PEG‐coated colloidal gold (CG) particles and 160 nm silica/gold nanoshells (NSs) in rats and rabbits. The above nanoparticles (NPs) were used as a model because of their importance for current biomedical applications such as photothermal therapy, optical coherence tomography, and resonance‐scattering imaging. The dynamics of NPs circulation in vivo was evaluated after intravenous administration of 15 nm CG NPs to rabbit, and the maximal concentrations of gold were observed 15–30 min after injection. Rats were injected in the tail vein with PEG‐coated NPs (about 0.3 mg Au/kg rats). 24 h after injection, the accumulation of gold in different organs and blood was determined by atomic absorption spectroscopy. In accordance with the published reports, we observed 15 nm particles in all organs with rather smooth distribution over liver, spleen and blood. By contrast, the larger NSs were accumulated mainly in the liver and spleen. For rabbits, the biodistribution was similar (72 h after intravenous injection). We report also preliminary data on the light microscopy and TEM histological examination that allows evaluation of the changes in biotissues after gold NPs treatment. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Targeting gene-virotherapy of cancer

Our purpose is to completely elimination of xenograft tumor in animal tumor model in order to work out a protocal for the cure of patient. Gene therapy and viral therapy for cancer have got some therapeutic effects, but both have no great breakthrough. Therefore, we worked out a new strategy called Targeting Gene-Virotherapy of Cancer which is a combination of the advantage of gene therapy and virotherapy. This new strategy has stronger antitumor effect than either of them alone. A tumor specific replicative adenovirus vector ZD55 (E1B 55KD deleted Adv.) which is similar to ONYX-015 in targeting fuction but significant different in construction was produced and various single therapeutic gene was inserted into ZD55. Now such a conception as Targeting Gene-Virotherapy of Cancer was raised and systemically studied before, although there are some works on ONYX-015-tk, -cd or cd/-tk etc. separately. The antitumor effect of ZD55-Gene (for example IL-24 gene) is much better than ZD55 (virotherapy) alone and hundred fold high than that of Ad-IL-24 (gene therapy) alone. ZD55-IL-24 was in preclinal studying in the ZD55-IL-24 therapy, completely elimination of tumor mass was occurred in some mice but not in all mice, that means one gene was not effictive enough to eliminate all the tumor mass in all mice. Therefore two genes with compensative or synergetic effect were inserted into ZD55 separately and used in combination. This strategy was called Targeting Dual Gene-Virotherapy of Cancer (with PCT patent). Then much better results were obtained and all the xenograft tumor masses were completely eliminated in all mice, if two suitable genes were chosen. On the basis of the initiation of two gene results, it was thought about that using two tumors promoter to control the virus vector will be better for the targeting effect and the safty of the drugs. Then double tumor controlled virus vector harboring two genes for cancer therapy was worked out. Better results have been obtained and another patent has been applied. This antitumor strategy could be used to kill all the tumor cells completely in all mice with minimum damage to normal cells.     

Targeting gene-virotherapy of cancer and its prosperity

Gene and viral therapies for cancer have shown some therapeutic effects, but there has been a lack of real breakthrough. To achieve the goal of complete elimination of tumor xenograft in animal models, we have developed a new strategy called Targeting Gene-Virotherapy of Cancer, which aims to combine the advantages of both gene therapy and virotherapy. This new strategy has produced stronger anti-tumor effects than either gene or viral therapy alone. A tumorspecific replicative adenovirus vector, designated as ZD55, was constructed by deletion of the 55kDa E1B region of adenovirus. The resulting viral construct not only retains a similar function to ONYX-015 by specifically targeting p53 negative tumors, but also allows for the insertion of various therapeutic genes to form appropriate ZD55 derivatives due to the newly introduced cloning site, a task not feasible with the original ONYX-015 virus. We showed that the anti-tumor effect of one such derivative, ZD55-IL-24, is at least 100 times more potent than that of either ZD55 virotherapy or Ad-IL-24 gene therapy. Nevertheless, complete elimination of tumor mass by the use of ZD55-1L-24 was only observed in some but not all mice, indicating that one therapeutic gene was not sufficient to ＂cure＂ these mice. When genes with complementary or synergetic effects were separately cloned into the ZD55 vector and used in combination （designated as the Dual Gene Therapy strategy）, much better results were obtained; and it was possible to achieve complete elimination of all the xenograft tumor masses in all mice if two suitable genes were chosen. More comprehensive studies based on this new strategy will likely lead to a protocol for clinical trial. Finally, the concept of Double Controlled Targeting Virus-Dual Gene Therapy for cancer treatment, and the implication of the recent progress in cancer stem cells are also discussed.     

肿瘤基因治疗的靶向策略

对肿瘤组织的靶向性可以提高基因治疗的效果 ,避免对正常组织的损伤 ,并且能降低作为载体的微生物对机体的危害。对于瘤内注射的给药方法 ,靶向性似乎显得不是特别重要 ,但是如果要系统给药 ,靶向性是很关键的一个问题。靶向基因治疗肿瘤可以通过靶向基因导入和靶向基因表达来实现。近年来 ,在靶向基因导入方面的研究有很多进展 ,例如 ,用双亲性的桥连分子协助腺病毒和逆转录病毒靶向转导 ;在各种病毒载体的衣壳蛋白中插入靶向性的小肽或较大的多肽靶向结构域 ;增殖病毒作为一种很有前途的抗肿瘤制剂可有效地靶向杀伤肿瘤细胞。受体介导的DNA或DNA 脂质体复合物的靶向系统和其他一些靶向性的有疗效的载体 ,如细菌 ,也处于研究中。其中的一些载体已经进入临床实验。为了实现基因的靶向可调控表达 ,组织或肿瘤特异性的启动子和人工合成的可调控表达系统被用来调控治疗基因的表达。反义核酸、核酶以及脱氧核酶 (DNAzyme)被用来靶向抑制与肿瘤发生密切相关基因的表达。     

二维过渡金属碳/氮化物在肿瘤治疗中的应用

二维过渡金属碳/氮化物（MXenes）具有优异的光热转换性能,丰富的表面基团,良好的生物相容性、亲水性和粒径可调性,这使得应用MXenes作为肿瘤诊疗过程中的治疗剂和造影剂具有巨大潜力。本文综述了基于MXenes的肿瘤单一治疗和联合治疗的相关研究,同时介绍了MXenes在肿瘤主动靶向治疗领域的研究,最后阐述了目前MXenes在制备和肿瘤治疗研究中存在的挑战和对未来的展望。