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。     

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。     

细胞-纳米药物载体递送系统在肿瘤诊疗中的应用

目前,针对肿瘤治疗药物在体内应用中的局限性,出现了许多高效的药物递送系统的研究,其中纳米药物载体技术和细胞药物载体技术较为热门,并取得了许多成果。纳米药物载体具有的优点,如防止药物发生降解及灭活,增加药物的靶向性,降低药物的毒副作用,可量产等。细胞载体更是利用细胞本身固有的特性,具有主动靶向肿瘤部位、低免疫原性和穿过体内生理屏障等优点,在药物递送研究中有广阔的应用前景,但是仍然存在很多问题及不足。研究人员创造性地将两者结合,使他们的优势互补,极大地强化了递送药的效率,增加了体内靶向性,降低了周围组织的细胞毒性等。本文从近几年来细胞-纳米药物载体系统研究的文献中,总结了红细胞、干细胞、单核/巨噬细胞、T细胞、树突状细胞（dendritic cell,DC）等作为纳米药物细胞载体的优缺点及目前的应用现状。     

新型纳米递送系统在药物诱导肿瘤细胞焦亡中的应用

随着纳米递送系统（NDS）研发的快速发展和对于细胞焦亡机制的深入认识,将两者巧妙结合而形成的肿瘤治疗新策略已经在部分肿瘤的实验性治疗中取得一定效果。基于NDS的药物诱导肿瘤细胞焦亡的策略,能够克服单独使用小分子焦亡诱导剂的缺陷,如体内清除快、全身不良反应严重及肿瘤靶向能力弱等。现已有脂质体、水凝胶、聚合物胶束、金属-有机框架（MOF）和仿生细胞膜的纳米载体等多种NDS被用于构建诱导肿瘤细胞焦亡的纳米药物复合体。在此基础上,目前已发展了多种基于NDS药物诱导肿瘤细胞焦亡的策略,包括靶向肿瘤干细胞、干扰离子稳态、促进ROS产生、诱导表观遗传学改变及递送gasdermin（GSDM）家族蛋白等。然而,这些策略要应用于临床治疗,还面临对纳米生物相互作用机制认知不够等问题。未来研究中,在全面了解纳米材料与生物系统的相互作用的基础上,如能开发新型、安全的NDS并结合有效的焦亡诱导剂,靶向诱导肿瘤细胞焦亡从而克服凋亡逃逸及多药耐药,则有望为肿瘤患者带来福音。     

基于金属有机框架材料的抗肿瘤药物递送与肿瘤治疗

金属有机框架材料（MOF）是一类由金属团簇或离子与有机支柱连接而成的混合多孔材料。由于具有孔道可调性、高孔隙率、大比表面积和良好的生物相容性,MOF可与多种生物大分子结合,近些年在生物医学领域的研究越来越广泛,尤其是在负载抗肿瘤药物方面展现出巨大的应用前景。结合不同治疗手段的多功能抗肿瘤MOF为肿瘤治疗提供了一种新的思路和方法。本文从MOF的结构出发,介绍了利用MOF负载抗肿瘤药物的优势,并对MOF在肿瘤治疗方面的应用研究进展进行综述。     

纳米药物应用于肿瘤治疗的研究进展

长期以来,大量研究致力于提高化疗效果,并且使患者的生存期大大延长,但是在化学治疗中仍存在很多问题有待进一步研究改进。在所有的因素中,与治疗效果直接相关的是药物对杀伤癌细胞的靶向能力和尽可能对正常细胞的影响最小。改善患者生存质量和最终的预期寿命的程度与治疗的靶向能力直接相关。近年来针对这一方向的研究包括对可控给药剂量和途径的载体开发,发现新的化疗靶点如供应肿瘤生长的血管系统和对其靶向治疗的研究,这些研究结果可使化疗在有效的同时更具有特异性。本综述将主要阐述纳米药物输送的新方法及最新的研究进展,着重于探讨与纳米粒子组成相关的具有特异性肿瘤靶向的纳米粒子的应用前景。     

透明质酸修饰的pH响应型阿霉素纳米递送系统靶向多发性骨髓瘤的体外研究

目的:构建一种特异性靶向多发性骨髓瘤的pH响应型纳米递送系统,实现对多发性骨髓瘤细胞靶向释放化疗药物阿霉素。方法:采用酸敏感的DSPE-PEOz和阳离子类脂DOTAP包封模型药物阿霉素（doxorubicin,DOX）,得到阿霉素纳米递送系统（DOX-NDS）,并经HA-PEG2000-DSPE（HA）靶向长循环修饰,最终制得阿霉素靶向纳米递送系统（DOX-HA-NDS）;纳米粒度电位仪分析DOX-HA-NDS的粒径和Zeta电位;多功能酶标仪检测DOX-HA-NDS的包封率（encapsulation efficiency,EE）和载药量（drug loading,DL）;透析法研究DOX-HA-NDS在pH 5.0和pH 7.4条件下的体外释药行为;流式细胞仪检测其细胞摄入;CCK-8法评价空白靶向纳米递送系统（Blank-HA-NDS）的毒性和DOX-HA-NDS的细胞增殖抑制作用。结果:构建的DOX-HA-NDS粒径为（193.1±5.0）nm,Zeta电位为（-41.1±2.0）mV,离心法和透析法测得包封率分别高达93%和90%,载药量为32.76%和32%,4 ℃存储能稳定6个月以上。在pH 7.4条件下,DOX-HA-NDS的释药缓慢,且6 h累积释放率仅为30%,而在pH 5.0条件下,DOX-HA-NDS的释药明显加快,6 h累积释放率高达97%,表明构建的阿霉素靶向纳米递送系统具有pH响应控释性能。细胞摄入实验结果表明,经HA修饰后的阿霉素纳米递送系统可以更有效靶向肿瘤细胞;体外抗肿瘤活性结果表明,Blank-HA-NDS基本无细胞毒性,DOX-HA-NDS对人多发性骨髓瘤细胞（ARH-77）的增殖抑制作用最强。结论:构建的阿霉素靶向纳米递送系统不仅包封率高,而且兼具主动靶向和pH响应控释性能,提高对DOX的输送效率,从而增强了其对ARH-77的细胞增殖抑制作用。     

载吲哚菁绿二氧化硅纳米颗粒的构建及其对宫颈癌HeLa细胞的杀伤作用

[摘要] 目的：构建载吲哚菁绿二氧化硅纳米颗粒（ICG@MSNs）并探讨其对宫颈癌HeLa细胞的杀伤作用。方法：通过模板法合成了介孔二氧化硅纳米颗粒（MSNs）,并物理包载光热剂吲哚菁绿（ICG）,制备具有光热效应的ICG@MSNs,并将其应用到HeLa细胞的体外研究中。结果：ICG@MSNs的粒径约200 nm,粒径均一,为形态规则的球形。ICG@MSNs与单纯的ICG具有类似的光热效应。细胞内吞实验显示,ICG包载于二氧化硅纳米颗粒后更易被肿瘤细胞内吞,进而发挥光热作用杀死宫颈癌HeLa细胞;细胞毒性实验表明,在808 nm激光照射下ICG@MSNs对细胞毒性作用明显增加,可以显著杀死宫颈癌HeLa细胞。结论：ICG@MSNs稳定性和生物相容性良好,同时具有良好的产热性能,肿瘤光热治疗效果明显,应用于宫颈癌治疗的前景良好     

抗肿瘤纳米药物载体的研究进展

目前在临床广泛应用的抗肿瘤药物多数为非选择性药物,为了提高药物疗效,减少毒副作用,人们对其超微粒子靶向、控释体系进行探索。载体材料必须是可生物降解的聚合物,包括天然和合成两类,可以为抗肿瘤药物治疗提供新的具有靶向功能的药物。本文就近年来抗肿瘤纳米药物载体的研究进展作一综述。     

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。     

PLGA-Based Nanoparticles as Cancer Drug Delivery Systems

Poly (lactic-co-glycolic acid) (PLGA) is one of the most effective biodegradable polymeric nanoparticles(NPs). It has been approved by the US FDA to use in drug delivery systems due to controlled and sustainedreleaseproperties, low toxicity, and biocompatibility with tissue and cells. In the present review, the structureand properties of PLGA copolymers synthesized by ring-opening polymerization of DL-lactide and glicolidewere characterized using 1H nuclear magnetic resonance spectroscopy, gel permeation chromatography,Fourier transform infrared spectroscopy and differential scanning calorimetry. Methods of preparation andcharacterization, various surface modifications, encapsulation of diverse anticancer drugs, active or passivetumor targeting and different release mechanisms of PLGA nanoparticles are discussed. Increasing experience inthe application of PLGA nanoparticles has provided a promising future for use of these nanoparticles in cancertreatment, with high efficacy and few side effects.     

Efficacy of Slow-releasing Anticancer Drug Delivery Systems on Transplantable Osteosarcomas in Rats

New drug delivery systems for cis-diamminedichloroplatinum (CDDP)incorporated into vehicles, such as polymethylmethacrylate (PMMA),fibrin glue (F.G.), alpha-tricalciumphosphate (TCP) and ethylenevinyleacetatecopolymer (Polymer) were examined using a rat osteosarcoma model.The materials containing CDDP were directly implanted into thetumors or subcutaneous tissue of rats, and the inhibitory effectson tumor growth and lung metastasis were evaluated. Data onin vitro kinetics of CDDP release revealed good results forboth TCP and F.G., and the release pattern from TCP to be mostappropriate for a slow-releasing drug delivery system. Thiswas supported by the results of the implantation experiments,whereby the direct implantation of TCP containing CDDP (CDDP-TCP)into tumors, gave significantly better inhibitions of tumorgrowth and metastasis than either non-treatment (P<0.01)or subcutaneous implantation (P<0.05). In a second experiment,using different administration procedures, different inhibitoryeffects on tumor growth and lung metastatic potency were observedwith intra-arterial and intravenous CDDP administration, aswell as with CDDP-TCP implanted subcutaneously. Suppressioneffects of CDDP (10 mg/kg)-TCP directly implanted into tumorswere equal to those of intra-arterial (2.5 mg/kg) and intravenous(5.0 mg/kg) administrations. The present results suggest CDDP-TCPimplantation to be effective as a slow-release drug deliverysystem for inhibiting tumor growth and metastasis, and thatit should be a useful adjuvant to conventional i.v. or i.a.chemotherapy.     

Physicochemical Characteristics of Fe3O4 Magnetic Nanocomposites Based on Poly(N-isopropylacrylamide) for Anti-cancer Drug Delivery

Background: Hydrogels are a class of polymers that can absorb water or biological fluids and swell to severaltimes their dry volume, dependent on changes in the external environment. In recent years, hydrogels and hydrogelnanocomposites have found a variety of biomedical applications, including drug delivery and cancer treatment.The incorporation of nanoparticulates into a hydrogel matrix can result in unique material characteristics suchas enhanced mechanical properties, swelling response, and capability of remote controlled actuation. Materialsand Methods: In this work, synthesis of hydrogel nanocomposites containing magnetic nanoparticles are studied.At first, magnetic nanoparticles (Fe3O4) with an average size 10 nm were prepared. At second approach, thermoand pH-sensitive poly (N-isopropylacrylamide -co-methacrylic acid-co-vinyl pyrrolidone) (NIPAAm-MAAVP)were prepared. Swelling behavior of co-polymer was studied in buffer solutions with different pH values(pH=5.8, pH=7.4) at 37˚C. Magnetic iron oxide nanoparticles (Fe3O4) and doxorubicin were incorporated intocopolymer and drug loading was studied. The release of drug, carried out at different pH and temperatures.Finally, chemical composition, magnetic properties and morphology of doxorubicin-loaded magnetic hydrogelnanocomposites were analyzed by FT- IR, vibrating sample magnetometry (VSM), scanning electron microscopy(SEM). Results: The results indicated that drug loading efficiency was increased by increasing the drug ratioto polymer. Doxorubicin was released more at 40˚C and in acidic pH compared to that 37˚C and basic pH.Conclusions: This study suggested that the poly (NIPAAm-MAA-VP) magnetic hydrogel nanocomposite couldbe an effective carrier for targeting drug delivery systems of anti-cancer drugs due to its temperature sensitiveproperties.     

经药盒系统对晚期肿瘤行化疗栓塞的临床研究

目的：采用介入技术经锁骨下动脉入路皮下植入药盒系统。研究经药盒系统对晚期肿瘤行化疗栓塞的临床疗效。方法：随机分成A、B两组。A组选择化疗栓塞的给药方案，B组选择单纯灌注化疗的给药方案，各20例。结果：两组有效率（CR＋PR）A组为45％，B组为20％（P＜0．05）。1年生存率A组为50％，B组为30％（P＜0．05）。结论：晚期肝癌患者，采用介入技术经锁骨下动脉入路皮下植入药盒系统行化疗栓塞是有效、可行的。     

埋植式药泵重复化疗栓塞治疗中晚期肝癌36例

［目的］总结埋植式药泵在重复化疗栓塞中的优越性。［方法］剖腹探查病理确诊后,经胃网膜右动、静脉分别置入埋植式药泵,反复多次地对肝癌进行化疗栓塞,最多者达１３次。［结果］３６例治疗后半年、１年、２年生存率分别为９１．６％、４７．２％及１９．４％,２例已带瘤生存分别超过３９和４８个月。［结论］应用埋植式药泵行重复肝动脉化疗栓塞治疗效果较好且经济、简便,并发症少。     

芒柄花黄素应用于抗癌药物开发的研究进展

 芒柄花黄素（Formononetin, FN）及其衍生物已被证明具有多种生物学功能，包括抗氧化、抗病毒和保护作用等，近年来它的抗癌活性得到国内外学者越来越多的关注。本文总结了芒柄花黄素在抗癌药物开发方面的研究进展，并探讨了当前存在的一些问题。     

纳米靶向给药在三阴性乳腺癌治疗中的研究进展

摘 要：近年来纳米医学作为交叉学科在肿瘤治疗中的运用进展迅速,纳米粒（nanoparticles,NPs）介导的靶向给药系统(drug delivery systems,DDS)已成为研究热点,其在肿瘤治疗中的关键方面是利用纳米载体靶向分子识别标记选择性地靶向肿瘤细胞,而不会对正常细胞或器官造成伤害。三阴性乳腺癌（triple negative breast cancer,TNBC）由于其特殊的分子分型,治疗困难,国际上虽无针对性的指南,但随着个性化肿瘤药物的快速发展,纳米给药平台为TNBC模块化、个性化治疗提供了更多的选择。全文讨论DDS在TNBC治疗中的进展。     

Research Progress on Long Non-coding RNAs and Drug Resistance of Breast Cancer

Breast cancer, as the foremost cause of women’s death in the world, is highly metastatic and mutable. Resistance to drugs for chemotherapies, endocrine therapies, and targeted therapies is an important factor that impacts the prognosis of breast cancer. Long non-coding ribonucleic acids (LncRNAs) are crucial regulators of intracellular gene expressions. Some researchers have suggested that expression level of several types of LncRNAs were closely related to the prognosis of patients with breast cancer. LncRNAs significantly impact biological processes such as drug transport, detoxication, apoptosis, epithelial to mesenchymal transition (EMT), and autophagy by regulating intracellular signaling pathways such as multi-drug resistance gene 1 (MDR1), nuclear factor erythroid 2-related factor 2 (NRF2), phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR), transforming growth factor-β (TGF-β), BRCA1/2, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). This paper will summarize research progress on correlations between LncRNA and drug resistance of breast cancer. It will particularly expound molecular mechanisms through which LncRNAs regulate drug resistance of breast cancer. It will further discuss the feasibility as molecular markers for forecasting drug resistance of breast cancer and may be becoming new targets for treating breast cancer in the future.     

茶黄素类天然产物抗肿瘤机制的研究进展

茶黄素类（Theaflavins）是从红茶或绿茶中提取的一类天然产物,在胃癌、肝癌及乳腺癌等多种肿瘤中具有显著的抗肿瘤效果,一度被认为是癌症新药研发的新方向。但是茶黄素抗肿瘤的机制涉及多种生物学过程,且调控复杂。因此,本文就茶黄素在促进肿瘤细胞凋亡、诱导肿瘤细胞有丝分裂阻滞和调节肿瘤免疫过程中的作用展开综述,并概述了茶黄素通过MAPK、PI3K/AKT、Hedgehog、NF-κB、JAK/STAT及Wnt/β-Catenin等信号通路抑制肿瘤发生和生长的机制,以期为癌症治疗及抗癌药物研发提供新的思路。