肿瘤穿透肽iRGD在肿瘤靶向纳米递药治疗中的研究进展

恶性肿瘤是目前严重威胁人类生命健康的重大疾病之一,随着对恶性肿瘤研究的深入,越来越多的抗肿瘤药物被研发应用并取得显著的成效,但是由于复杂的肿瘤微环境,抗肿瘤药物常难以渗透至肿瘤组织深部,导致生物利用度低,抗肿瘤作用减弱。肿瘤穿透肽（tumor-penetrating peptide）iRGD化学连接在纳米载体表面或者与纳米载体联合给药,促进药物渗透至肿瘤组织深部有效发挥抗肿瘤作用,是目前肿瘤靶向治疗领域中备受关注的研究方向之一。本文回顾并总结了iRGD在抗肿瘤靶向纳米递药治疗中的研究进展,这些研究结果都显示了肿瘤穿透肽iRGD在肿瘤靶向治疗中拥有良好的应用前景。     

携带磁性纳米颗粒载药微囊的制备及肿瘤治疗的应用研究进展

通过磁场操控使携带磁性纳米颗粒的微囊富集在生物体特定部位,可实现微囊对特定组织或器官的靶向输送。负载抗肿瘤药物的磁性微囊既可以磁靶向到肿瘤组织,又有缓释、控释药物的优点,已成为实现肿瘤靶向治疗的新型药物载体。本文综述了脂质体、聚合物电解质微囊、聚合物微球等药物载体携带磁性纳米颗粒的制备方法,及其用于抗肿瘤药物载体的基础研究进展。      

激发性金属纳米疗法抗肿瘤作用的研究进展

纳米医学利用直径1～100 nm粒子的优势,将纳米技术广泛应用于多个生物医学领域.激发性金属纳米疗法是纳米医学的一个重要领域,在肿瘤治疗领域发挥着开创性作用.激发性金属纳米疗法基于金属纳米粒子与激发分子的相互作用,激发的方式包括内部激发、外部激发及联合激发,主要抗肿瘤形式包括化学动力治疗、光热治疗、光动力治疗、磁热治疗、联合免疫治疗等.内部激发分子触发的金属纳米疗法被广泛用于安全有效的抗肿瘤药物传递;外部激发分子具有可调控的特点,适用于抗肿瘤药物的靶向递送与肿瘤的精准靶向治疗;内部激发分子与外部激发分子联合的金属纳米疗法为肿瘤的联合治疗提供了新思路.本文就激发性金属纳米疗法在抗肿瘤治疗中的研究进展展开综述.     

细菌介导的肿瘤协同治疗策略

随着基因工程和合成生物学的快速发展,以及对宿主病原体相互作用的认识更加深入,细菌在肿瘤治疗中的作用被广泛研究。细菌介导的肿瘤治疗机制主要包括肿瘤特异性靶向、诱发抗肿瘤免疫反应等,通过与化疗、放疗等传统疗法的结合,可以提高抗肿瘤疗效,同时降低对宿主的全身毒性。利用基因工程可获得对肿瘤组织更高靶向性的减毒菌株或细菌衍生物,从而提高肿瘤治疗的有效性和安全性。此外,细菌表面的可修饰性和表面化学偶联的多样性对实现理想载药及多模式抗肿瘤治疗成为可能,尤其是纳米载药体系与细菌结合组装的生物复合纳米递送系统,可克服传统纳米药物靶向性低、难以渗透到肿瘤深部组织的不足。尽管细菌用作抗肿瘤及释药体系的运输载体仍然有很多亟待解决的问题,但细菌在肿瘤区域特异性定植并诱导肿瘤免疫反应的特性以及作为理想药物载体的潜力,为肿瘤治疗提供了一个颇有前景的新范式。     

纳米粒子药物输送系统与实体脑肿瘤的诊断和治疗

目前,对包括多形性成胶质细胞瘤在内的脑肿瘤的治疗效果不佳。血脑屏障限制了放化疗药物以有效的浓度到达肿瘤细胞。常用的方法是通过外科手术切除大部分肿块及对浸润部分的辅助治疗,以多功能纳米粒子为基础的药物输送系统(drug delivery system,DDS)的发展为实体脑肿瘤的诊断和治疗提供了新的思路。以氧化铁、量子点等为代表的纳米粒子可以作为核磁共振成像(magnetic resonance imaging,MRI)探针、光学探针以及结合多种成像方法的探针为实体脑肿瘤的诊断提供更加敏感的分辨能力和更加清晰的成像。此外,多柔比星、紫杉醇等化疗药物的肿瘤内输送,也从最初的脂质体转运系统和多聚物组成的非磷脂纳米粒逐步发展到兼具多种功能的新型纳米粒子转运治疗系统。通过改变其大小、组成和表面化学性质,纳米粒子能够发展成为结合检测、成像、药物靶向导入的多功能平台,尤其是靶向分子修饰的纳米粒子,在实体脑肿瘤的治疗中具有极大的发展前景。本文针对利用纳米粒子进行诊断和治疗脑肿瘤的最新研究进展作一综述,并展望其在肿瘤治疗领域的发展前景。     

基于肿瘤微环境的基因给药纳米载体的研究进展

近年来基因给药系统在肿瘤治疗中的研究备受关注。纳米载体具有增强药物靶向性、增加生物膜通透性、控制药物释放速度、提高生物利用度和可承载生物大分子等优点。由于肿瘤的快速增殖和代谢,形成了具有低pH、高水平谷胱甘肽、高水平活性氧、缺氧性、高表达酶和高水平ATP等特性的肿瘤微环境（TME）。基于肿瘤组织特异性微环境的基因给药纳米载体能同时提高基因药物的胞外稳定性、胞内释放能力和靶向性,可更大程度地提高药物的抗肿瘤作用、减少不良反应的发生。本文对基于TME的pH响应型、还原响应型、活性氧响应型、缺氧响应型、酶响应型、ATP响应型和多智能响应型纳米载体进行综述,总结各类型纳米载体的作用机制、制备、抗肿瘤效果及局限性。基因给药纳米载体可提高基因的转染效率,提高抗肿瘤作用,在抗肿瘤应用中有较好的前景。     

超声纳米微泡造影剂在肿瘤诊疗中的研究进展

随着分子生物学的快速发展,超声纳米微泡造影剂已成为研究热点之一。其作为一种新型的造影剂具有纳米级粒径,在成像方面有多种优势,容易实现对肿瘤的靶向性,在肿瘤诊疗中有一定意义。超声纳米微泡造影剂不仅可以结合超声成像、荧光探针及铁粒子等增强成像效果,还可以包裹肿瘤靶向药物进行药物靶向递送、作为载体和免疫增强剂携载目的基因进行基因转染、促进肿瘤的免疫治疗,为肿瘤的诊断和治疗提供了新方法。本文针对超声纳米微泡造影剂在肿瘤中的研究进展进行综述。     

纳米药物递呈系统与肿瘤的研究进展

纳米药物提呈系统能同时检测多种肿瘤标记物，是选择性肿瘤成像的有力载体，被广泛用于肿瘤的诊断。纳米药物递呈系统使抗肿瘤药物具有靶向性、低毒高效、稳定性的特点，并能延缓药物的释放。在基因治疗方面，纳米药物提呈系统发挥着越来越重要的作用。随着纳米技术的发展，纳米药物提呈系统将在肿瘤诊断和治疗方面具有广阔的应用前景。     

主动靶向磁纳米载体在肿瘤治疗中的研究进展

主动靶向磁性纳米载体作为一种新的预防、诊断和治疗肿瘤的方法为肿瘤的防治取得了开拓性的进展.可通过在磁性纳米粒子表面选择性修饰特异性介导分子构建具有靶向性结合能力的纳米粒子,实现主动靶向于肿瘤细胞的目的.目前,主动靶向磁性纳米粒子已用于肿瘤热疗、药物治疗和免疫检测等方面.     

超顺磁性氧化铁纳米粒子诊断与治疗乳腺癌的研究进展

在乳腺癌的诊疗过程中，常规药物存在靶向性较差和严重的不良反应等缺陷。近年来，具有高选择性及优异成像性能的超顺磁性氧化铁纳米粒子（SPION）已成为影像学领域的研究热点。SPION 是一种具有磁性的纳米材料，其以氧化铁为核心，置于较弱的外磁场中就可产生较强的磁性。新型SPION 具有尺寸小、生物相容性好、制备流程简单和生产成本低等优点，且具有较好的磁响应能力，有望作为医学成像探针和药物靶向递送系统的载体，在提高肿瘤影像学特异性诊断和实现更精确给药等方面都具有良好的医学应用前景。在乳腺癌影像学诊断和治疗中，SPION 可作为分子靶向造影剂用于磁粒子成像观察，还可应用于化疗药物递送、基因传递、免疫治疗和光动力治疗等。随着以SPION为核心的临床试验进一步开展，SPION在乳腺癌诊疗中的应用将进一步拓展。     

Nanomedicine for drug delivery and imaging: a promising avenue for cancer therapy and diagnosis using targeted functional nanoparticles

The diagnosis and treatment of cancer or tumor at the cellular level will be greatly improved with the development of techniques that enable the delivery of analyte probes and therapeutic agents into cells and cellular compartments. Organic and inorganic nanoparticles that interface with biological systems have recently attracted widespread interest in the fields of biology and medicine. The new term nanomedicine has been used recently. Nanoparticles are considered to have the potential as novel intravascular or cellular probes for both diagnostic (imaging) and therapeutic purposes (drug/gene delivery), which is expected to generate innovations and play a critical role in medicine. Target-specific drug/gene delivery and early diagnosis in cancer treatment is one of the priority research areas in which nanomedicine will play a vital role. Some recent breakthroughs in this field recently also proved this trend. Nanoparticles for drug delivery and imaging have gradually been developed as new modalities for cancer therapy and diagnosis. In this article, we review the significance and recent advances of gene/drug delivery to cancer cells, and the molecular imaging and diagnosis of cancer by targeted functional nanoparticles.     

分子印迹聚合物在抗肿瘤药物传递系统中的研究进展

本文围绕分子印迹聚合物（molecularly imprinted polymer,MIP）在抗肿瘤药物传递系统（drug delivery system,DDS）中的应用进行综述，介绍了分子聚合物的方法及提高分子印迹聚合物载药量和联合给药的策略，从内源和外源性敏感刺激的角度分析了分子聚合物在抗肿瘤药物传递系统的应用，并指出分子聚合物作为抗肿瘤药物的载体目前仍存在的生物相容性和可降解性问题,展望了分子聚合物在抗肿瘤药物传递系统应用中的前景及发展方向。     

纳米粒作为抗肿瘤药物载体的研究进展

纳米粒载药系统可以改变药物的体内分布特征, 具有缓控释和靶向给药特性, 增加药物的稳定性, 提高药物的生物利用度。纳米粒的靶向选择性可以通过增强渗透滞留效应(EPR)、偶联特定的配体, 或由于生理条件如pH值、温度等的改变实现。纳米粒可以由多种材料制备并且用于包合各种化学治疗药物以降低药物不良反应, 其中, 磁性纳米粒作为抗肿瘤药物载体不仅可以用来治疗还能用于成像诊断。本文综述了纳米粒被动靶向、主动靶向、物理化学靶向给药系统用于抗肿瘤药物载体的研究进展。      

In vivo single molecular fluorescence imaging for analysis of pharmacokinetics

Nano-materials are expected for research on molecular imaging of pharmacokinetics. We measured in vivo migration of CdSe nano-particles(Quantum Dots(QDs))conjugated with monoclonal anti-HER2 antibody(trastuzumab)in tumor vessel to breast cancer cells. We established a high resolution in vivo 3D microscopic system for a novel imaging method at single molecular level. The HER2 protein expressed in cancer cells and its dynamics were visualized by QDs in vivo at the spatial resolution of 30 nm. It suggests future utilization of the system in medical applications to improve the drug delivery system to target primary and metastatic tumors for made-to-order treatment. Future innovation in cancer imaging by nano-technology and novel measurement technology will provide great improvement, not only in the clinical field, but also in basic medical science. Advances in nano-biotechnology have great potential to improve prevention, diagnosis and treatment of human disease.     

Magnetic resonance pharmacoangiography to detect and predict chemotherapy delivery to solid tumors

Detection and prediction of drug delivery to the tumor interstitium are of critical importance in cancer chemotherapy. Prediction of drug delivery derived from standard pharmacokinetic models is frequently inadequate because of the complex nature of tumor blood flow and the microenvironment. Although drug concentrations can be directly sampled with microdialysis or in biopsy samples, we currently lack methods capable of detecting and/or predicting drug delivery to tumors noninvasively. In this study, we describe a novel magnetic resonance (MR) technique to directly detect the drug, and we present the correlation between delivery of drug and the delivery of MR contrast agents to the tumor. Experiments were performed with tumor xenografts in severe combined immunodeficient mice. Three-dimensional maps of the drug distribution within the tumors were obtained with 13C spectroscopic MR imaging with a spatial resolution of 2 x 2 x 2 mm, using signals of the 13C-labeled anticancer agent phenylacetate. Three-dimensional maps of uptake of gadolinium-diethylenetriaminepentaacetic acid (GdDTPA) contrast agent were obtained for the same tumors using dynamic MR imaging. Experimental data were analyzed for correlation between delivery of the drug and the contrast. Histological analysis was performed for excised tumors. Experimental data demonstrated a significant spatial correlation (r = 0.59 with P < 0.001) between the parameter representing delivery of the contrast to tumor interstitium, determined from the kinetic curves of GdDTPA, and integral tissue drug concentrations for two different tumor models. The method is designed to probe extravasation of the drug molecules from the bloodstream into the tumor interstitium. Although therapeutic efficiency of the drug will also depend upon drug retention in the tumor and the ability of the molecules to cross cellular membranes, inefficient drug transfer from plasma to tissue can be a major impediment in achieving effective tumor chemotherapy. The results of this study demonstrate that the uptake kinetics of a low molecular weight MR contrast agent can be used to predict delivery of drug molecules of similar size to the interstitium of solid tumors.     

量子点荧光成像在肿瘤诊治应用研究进展

量子点(quantum dot,QD),又名“人造原子”,是一种用原子人工合成的纳米材料,其在紫外光激发下可发出不同波长的荧光.QD直径小、发出的荧光峰窄、荧光亮度持久,具有取代有机染料用于肿瘤诊治的潜能.总结近年QD在荧光成像及肿瘤诊治方面的研究进展.方法 应用PubMed及中国知网(CNKI)数据库检索系统,以“quantum dots,fluorescence imaging,oncotherapy,tumor therapy,量子点,肿瘤治疗,肿诊断,荧光成像”为关键词,检索2005-01-2016-03的相关文献391篇.纳入标准:(1)可用于生物荧光成像的低毒化QD;(2)靶向识别的功能化QD.根据纳入标准最终分析31篇文献.结果 低毒化QD在细胞成像、活体靶向成像、淋巴结成像、活体肿瘤成像、活体肿瘤细胞示踪等荧光成像方面的研究,使正确定位淋巴结、利用QD深成像能力发现极小的肿瘤、乃至彻底切除肿瘤组织成为可能.功能化QD在肿瘤早期诊断和治疗上发挥更大作用,QD的药物靶向和QD介导的光热治疗肿瘤也有很好的临床应用前景.结论 QD在生物荧光成像及肿瘤诊疗中的潜力巨大,具有进一步探索开发利用于临床的价值.     

Radiation-guided drug delivery systems

A primary limiting factor for cancer treatment is normal tissue toxicity. Targeted cancer treatment can potentially maximize cancer cure and minimize normal tissue toxicity. Physical energy can be used to activate inert oncologic drugs. X-rays have an advantage over other forms of physical energy because tissue penetration and precise localization can be achieved. Radiation can be used to control drug delivery through radiation-inducible gene therapy. Radiation-guided drug delivery systems involve the targeting of immunoconjugates to radiation-inducible neoantigens induced by irradiation of neoplasms. Magnetic fields can compliment these technologies by drawing magnetic particles containing oncologic drugs toward an externally applied magnetic field. The field of targeted drug delivery by use of external radiation fields will ultimately bring new delivery systems into clinical trials. This review highlights radiation-guided cancer drug delivery systems, at preclinical and clinical stages of development, to tumors and tumor blood vessels.     

Nanoscale Au@SiO2-drug/VEGF as an in vivo probe for osteosarcoma diagnosis and therapy

Osteosarcoma is a common primary bone malignancy, with a 5-year survival rate of only 20–30% in patients undergoing surgical treatment. Thus, it is important to identify novel methods for diagnosing and treating osteosarcoma, which was the aim of the present study. Vascular endothelial growth factor (VEGF) was used as the tumor-targeting protein to synthesize a multifunctional core-shell nanostructure, Au@SiO₂-drug/VEGF, in which the drug can be indocyanine green (ICG; as an optical tracer) or doxorubicin (DOX; as a chemotherapeutic agent). With VEGF as the osteosarcoma-targeting protein, Au exhibited optimal photothermal transformation performance, while SiO₂ served as the carrier for the drug. Au@SiO₂-ICG/VEGF nanoparticles (NPs) were evaluated for imaging and for the monitoring of drug accumulation in a tumor region in mice. Once the optimal drug accumulation was achieved, combined treatment of osteosarcoma (chemotherapy and photothermal therapy) was assessed. In the perioperative period associated with minimal invasive embolization of osteosarcoma, photothermal therapy and chemotherapy were applied for osteosarcoma diagnosis using Au@SiO₂-DOX/VEGF NPs. Taken together, the results of the present study provide a promising strategy for tumor detection prior to surgical treatment to improve the survival outcome of patients with osteosarcoma.     

Radiation-guided drug delivery systems

A primary limiting factor for cancer treatment is normal tissue toxicity. Targeted cancer treatment can potentially maximize cancer cure and minimize normal tissue toxicity. Physical energy can be used to activate inert oncologic drugs. X-rays have an advantage over other forms of physical energy because tissue penetration and precise localization can be achieved. Radiation can be used to control drug delivery through radiation-inducible gene therapy. Radiation-guided drug delivery systems involve the targeting of immunoconjugates to radiation-inducible neoantigens induced by irradiation of neoplasms. Magnetic fields can compliment these technologies by drawing magnetic particles containing oncologic drugs toward an externally applied magnetic field. The field of targeted drug delivery by use of external radiation fields will ultimately bring new delivery systems into clinical trials. This review highlights radiation-guided cancer drug delivery systems, at preclinical and clinical stages of development, to tumors and tumor blood vessels.     

循环miRNAs在肺癌诊断和治疗中的研究进展

肺癌是全世界男性和女性癌症死亡的第一原因。尽管近些年对癌症信号通路的了解和在新的治疗方法开发上有了新进展,但是肺癌的不良预后和高复发率依然存在。循环miRNAs在许多实体瘤（如肺癌）中,可作为稳定表达的非侵入性诊断标志物。一些miRNAs异常可能与肿瘤细胞常规化疗的耐药性有关,影响着肿瘤细胞的药物敏感性。这些miRNAs的调控,通过使用miRNAs类似物,可以调节关键基因网络和信号通路,通过抑制肿瘤细胞增殖来提高抗癌治疗的疗效,增加药物敏感性。因此,miRNAs疗法提供了新的抗肿瘤方法:更有效的个性化治疗、提高药物疗效、预测不同抗癌药物的反应。本综述的目的是为肺癌循环miRNA提供一个作为潜在诊断生物标志物、大规模临床筛选诊断的可行性评估以及miRNAS抗癌耐药机制对肺癌的治疗的概述。最后,miRNA分析的局限性和潜在性需要今后进一步探索。