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癌症一直是危害人类健康的主要疾病之一。传统的癌症治疗方法包括放疗、化疗和手术,均具有明显的毒副作用或局限性。脂质体和纳米颗粒作为被广泛研究的药物递送载体,在人体临床试验中也出现了药物渗漏和装载功能不全等问题。目前而言,应用具有肿瘤靶向性的载体递送抗肿瘤药物或小分子,是有希望介导安全、有效的肿瘤治疗的策略之一。近年来,细菌来源的非复制型小细胞已受到越来越多的关注。小细胞是细菌异常分裂时期产生的纳米级无核细胞,其直径为200–400 nm,因而具有较大的药物装载能力。对小细胞的表面进行修饰,例如,装配能与肿瘤细胞表面特异性抗原或受体结合的抗体/配体,可显著提高小细胞的肿瘤靶向性。这种具有靶向性的纳米材料能将抗肿瘤的化疗药物、功能性核酸或编码功能性小分子的质粒靶向递送至肿瘤,而减少药物在正常组织器官的集聚。因此,使用小细胞作为靶向递送载体有助于降低药物对机体的毒性,从而最大限度地发挥药物分子在体内的抗肿瘤活性。文中将对小细胞的产生与纯化、药物装载、肿瘤细胞靶向性、内化过程以及其用于递送抗肿瘤药物的研究进展等方面进行综述,为开发基于小细胞的癌症治疗策略提供一定的参考。 相似文献
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介孔二氧化硅因具有有序介孔结构、比表面积大、生物相容性好及表面易于修饰等特点, 在生物医药等领域显示出了极大的应用前景, 目前, 基于介孔二氧化硅的纳米药物输送体系已成为众多科研工作者研究的热点. 本文讨论了靶向修饰及成像等多功能化的介孔二氧化硅药物输送体系的研究进展, 同时详细介绍了一系列具有特定形态结构(如中空/摇铃状、纳米管等)的介孔二氧化硅基载药体系的制备、表面修饰及在其在药物输送、释放等领域的应用研究. 最后, 对目前介孔二氧化硅基药物输送体系(主要包括具有特定形态结构的介孔二氧化硅药物载体、多功能复合药物载体及可生物降解的介孔二氧化硅药物输送体系等)在实际应用中存在的问题进行了分析并对其未来的发展前景进行了展望. 相似文献
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传统的肿瘤治疗方法因缺乏足够的靶向性而会产生严重的毒副作用。外泌体(exosome)是一种天然的纳米囊泡,参与细胞间的信息传递,并且作为药物递送载体具有出色的性能优势,包括低免疫原性、低毒性和能够穿越天然屏障等特点。然而以外泌体为载体的药物递送系统的靶向能力仍有不足。适配体(aptamer)是一类化学合成的单链核酸分子,具有分子质量小、易于修饰和免疫原性低等特点,可作为亲和性配体与靶向分子特异性结合。通过在外泌体表面修饰适配体,药物可以被精确递送到肿瘤细胞发生部位,从而实现对肿瘤的靶向治疗,提高肿瘤治疗效果,减少毒副作用。本篇综述将重点讨论适配体功能化外泌体药物靶向递送系统在各种肿瘤治疗方面的应用,并对其未来的挑战和机遇进行阐述。 相似文献
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介孔二氧化硅纳米粒子(mesoporous silica nanoparticles,MSNs)作为新型纳米载体在生物医药领域具有较好的应用前景,其有别于传统无机材料的物理化学性质对于当今恶性肿瘤的诊断与治疗起着关键性作用。尤其是MSNs作为一种具有高装载量、良好的生物相容性、靶向性以及对药物释放的可控性的载药平台,可用于解决目前临床上恶性肿瘤诊疗中遇到的问题。主要探讨了MSNs探针及MSNs靶向给药系统的应用进展及发展方向,以期为恶性肿瘤诊疗提供思路与参考。 相似文献
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《中国科学:生命科学》2016,(11)
纳米载体靶向药物递送系统早已受到各国的广泛关注,虽然这一研究方向的论文发表量呈指数增加,却基本没有成药性.本文基于物理化学和生物学原理分析,通过对不同材料和粒径纳米载体扩散系数的实验研究,探讨分子与纳米粒子在水介质中依数性和扩散能力的差异、纳米载体在体内的寻靶过程,从根本上剖析了纳米载体靶向药物递送系统理论中存在的种种误区,揭示了主动靶向修饰的纳米载体并不能够按照载体设计的初衷提高对肿瘤组织的靶向效率的缺陷.证明EPR效应只适用于药物分子与具有足够扩散能力的纳米载体,并提出依靠环境特异性响应的靶向释药、提高纳米载体扩散能力、利用巨噬细胞固有的吞噬作用捕获NPs实现靶向药物递送以及逐级靶向等更具有可行性的靶向递送新策略. 相似文献
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纳米载药体系作为一类具有可控性和靶向性的药物递送工具,可以保护生物分子药物免于细胞内快速酶促降解、免于快速血液清除,确保将生物分子药物安全递送至作用部位,从而有效改善药物的生物利用度,提高药物疗效并降低毒副作用,在生物医学领域具有广阔的应用前景,在功能材料研究和肿瘤靶向治疗研究中受到广泛关注.近年来,通过使用功能性生物... 相似文献
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目的:肿瘤的多药耐药现象会显著降低肿瘤细胞内药物浓度,本研究通过制备抗肿瘤多药耐药的靶向给药系统来逆转肿瘤的耐药性以提升细胞对药物的敏感性,从而降低该现象对癌症治疗的阻碍。方法:本文使用乳化溶剂挥发法制备以含姜黄素两亲性嵌段共聚物载体、以紫杉醇和磁性粒为核心的抗肿瘤多药耐药纳米粒,使用透射电镜和动态粒径散射仪等对纳米粒进行表征和磁响应性测试后,使用MTT法测定纳米粒对肿瘤耐药细胞MCF-7/ADR的抑制率以探究给药系统的耐药逆转性能。结果:制备的抗肿瘤多耐药纳米粒粒径为105 nm左右,磁响应性良好。所制得载紫杉醇纳米粒包封率为74.74%,载药率为12.40%。纳米粒可以通过磁场和生物素受体介导作用促进肿瘤细胞对粒子的内化,以增加抗癌药物的蓄积。与游离紫杉醇相比,逆转细胞耐药指数达8.5。结论:纳米系统在维持自身稳定性同时,能够凭借协同作用和靶向作用较大程度提升药物对耐药肿瘤细胞的杀伤效果。 相似文献
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肝癌动物模型是抗肝癌药物实验及肝靶向给药系统验证的重要方法和手段。本文对用于研究肝靶向制剂的动物模型的种类、特征、不足及应用进行了研究论述,提出了目前较适于应用的模型,应用肝癌动物模型可以提供与肝癌病人相似的肝癌生物学特性,也为肝靶向给药制剂药代动力学指标的可靠性提供了保障。 相似文献
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Angiogenesis is an important process in cancer growth and metastasis. During the tumor angiogenic process, endothelial cells express various cell surface receptors which can be utilized for molecular imaging and targeted drug delivery. One such protein receptor of interest is the integrin alphav beta3. Our group is involved in the development of molecular imaging probes and drug delivery systems targeting alphav beta3. Based on extensive lead optimization study with the integrin antagonist compounds, we have developed a new generation of integrin alphav beta3 compound (IA) which has superior binding affinity to alphav beta3. Utilizing this IA as a targeting agent, we have developed a novel integrin-targeted nanoparticle (ITNP) system for targ alphav beta3 was observed. These ITNPs also were rapidly taken up by cells that express alphav beta3. The ITNPs accumulated in the angiogenic vessels, after systemic administration in a murine squamous cell carcinoma model. This novel intergrin targeted ITNP platform will likely have an application in targeted delivery of drugs and genes in vivo and can also be used for molecular imaging. 相似文献
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S. Sripriyalakshmi Pinkybel Jose Aswathy Ravindran C. H. Anjali 《Cell biochemistry and biophysics》2014,70(1):17-26
Engineered nanoparticles that can facilitate drug formulation and passively target tumours have been under extensive research in recent years. These successes have driven a new wave of significant innovation in the generation of advanced particles. The fate and transport of diagnostic nanoparticles would significantly depend on nonselective drug delivery, and hence the use of high drug dosage is implemented. In this perspective, nanocarrier-based drug targeting strategies can be used which improve the selective delivery of drugs to the site of action, i.e. drug targeting. Pharmaceutical industries majorly focus on reducing the toxicity and side effects of drugs but only recently it has been realised that carrier systems themselves may pose risks to the patient. Proteins are compatible with biological systems and they are biodegradable. They offer a multitude of moieties for modifications to tailor drug binding, imaging or targeting entities. Thus, protein nanoparticles provide outstanding contributions as a carrier for drug delivery systems. This review summarises recent progress in particle-based therapeutic delivery and discusses important concepts in particle design and biological barriers for developing the next generation of particles drug delivery systems. 相似文献
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对精准医疗即个体化医疗理念的探讨与实践是当下医学研究的热门课题,如果精准医疗的设想实现可为患者提供更加精确有效的治疗方案,而对癌症的研究是医学界尚未攻破且意义重大的研究课题,也是和精准医疗结合最密切的课题之一。应用生物信息学的计算方法可以通过分析患者的概况来为癌症患者的药物选择提供有效方案,从而提高癌症患者的生存率。通过参考多篇使用计算方法研究抗癌药物作用的研究成果,从数据源和网络分析、机器学习和深度学习等计算方法两个方面总结了当前的研究成果,并对该课题存在的问题与未来发展趋势做出了分析与展望。 相似文献
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Fatemeh Yarian Abbas Alibakhshi Shirin Eyvazi Roghaye Arezumand Shahrzad Ahangarzadeh 《Journal of cellular physiology》2019,234(10):16724-16738
Codelivery is a promising strategy of targeted delivery of cytotoxic drugs for eradicating tumor cells. This rapidly growing method of drug delivery uses a conjugate containing drug linked to a smart carrier. Both two parts usually have therapeutic properties on the tumor cells. Monoclonal antibodies and their derivatives, such as Fab, scFv, and bsAb due to targeting high potent have now been attractive candidates as drug targeting carrier systems. The success of some therapeutic agents like small interfering RNA (siRNA), a small noncoding RNAs, with having problems such as enzymatic degradation and rapid renal filtration need to an appropriate carrier. Therefore, the aim of this study is to review the recent enhancements in development of antibody drug conjugates (ADCs), especially antibody–siRNA conjugates (SRCs), its characterizations and mechanisms in innovative cancer therapy approaches. 相似文献
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Ambikesh Soni Manohar Prasad Bhandari Gagan Kant Tripathi Priyavand Bundela Pradeep Kumar Khiriya Purnima Swarup Khare Manoj Kumar Kashyap Abhijit Dey Balachandar Vellingiri Suresh Sundaramurthy Arisutha Suresh José M. Pérez de la Lastra 《Journal of cellular and molecular medicine》2023,27(6):737-762
In recent years, drug manufacturers and researchers have begun to consider the nanobiotechnology approach to improve the drug delivery system for tumour and cancer diseases. In this article, we review current strategies to improve tumour and cancer drug delivery, which mainly focuses on sustaining biocompatibility, biodistribution, and active targeting. The conventional therapy using cornerstone drugs such as fludarabine, cisplatin etoposide, and paclitaxel has its own challenges especially not being able to discriminate between tumour versus normal cells which eventually led to toxicity and side effects in the patients. In contrast to the conventional approach, nanoparticle-based drug delivery provides target-specific delivery and controlled release of the drug, which provides a better therapeutic window for treatment options by focusing on the eradication of diseased cells via active targeting and sparing normal cells via passive targeting. Additionally, treatment of tumours associated with the brain is hampered by the impermeability of the blood–brain barriers to the drugs, which eventually led to poor survival in the patients. Nanoparticle-based therapy offers superior delivery of drugs to the target by breaching the blood–brain barriers. Herein, we provide an overview of the properties of nanoparticles that are crucial for nanotechnology applications. We address the potential future applications of nanobiotechnology targeting specific or desired areas. In particular, the use of nanomaterials, biostructures, and drug delivery methods for the targeted treatment of tumours and cancer are explored. 相似文献
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甲胎蛋白(alpha fetoprotein, AFP)是一种在胎儿发育时期高表达的蛋白质,它又是一种穿梭蛋白质,能够将营养物质输送给胚胎细胞。相似的是,在肝癌等恶性肿瘤发展时期,肿瘤细胞也高表达AFP及其受体,它们通过AFP受体摄取AFP及其运载的物质。因此,可以将AFP与抗癌药物结合,选择性攻击肿瘤细胞。AFP与药物的结合方式有多种,它可以和药物非共价结合,药物被包裹在AFP的疏水袋中;也可以通过共价键与药物结合,或者利用AFP与纳米颗粒和脂质体连接来提高输送药物的效果,肿瘤细胞的酸性环境能促使结合的药物有效释放。为了避免AFP致癌的风险,还可以通过改造AFP或利用AFP片段来输送药物。由于AFP介导的肿瘤靶向治疗主要是攻击具有AFP受体的癌细胞,因此对正常细胞影响并不大。AFP携带药物不仅能促进肿瘤细胞对药物的吸收、提高药物的抗肿瘤活性,还能克服多重耐药(multidrug resistance, MDR)问题。另外,AFP携带药物还具有免疫治疗的效果。AFP携带药物不仅能激活T细胞受体,消除免疫耐受,抑制肿瘤的生长,还能利用改造好的AFP靶向抑制髓源性抑制细胞(myeloid-derived suppressor cells, MDSCs),激活NK细胞和T细胞,从而破坏癌细胞以及阻止癌干细胞的转移。因此,AFP携带药物治疗是免疫治疗与靶向化疗相结合的新疗法,它将成为治疗癌症的一种策略。 相似文献
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Yan A. Ivanenkov Alexey E. Machulkin Anastasia S. Garanina Dmitry A. Skvortsov Anastasia A. Uspenskaya Ekaterina V. Deyneka Alexander V. Trofimenko Elena K. Beloglazkina Nikolay V. Zyk Victor E Koteliansky Dmitry S. Bezrukov Anastasia V. Aladinskaya Nataliya S. Vorobyeva Maria M. Puchinina Grigory K. Riabykh Alina A. Sofronova Alexander S. Malyshev Alexander G. Majouga 《Bioorganic & medicinal chemistry letters》2019,29(10):1246-1255
Prostate-specific membrane antigen (PSMA), also known as glutamate carboxypeptidase II (GCPII), has recently emerged as a prominent biomarker of prostate cancer (PC) and as an attractive protein trap for drug targeting. At the present time, several drugs and molecular diagnostic tools conjugated with selective PSMA ligands are actively evaluated in different preclinical and clinical trials. In the current work, we discuss design, synthesis and a preliminary biological evaluation of PSMA-specific small-molecule carrier equipped by Doxorubicin (Dox). We have introduced an unstable azo-linker between Dox and the carrier hence the designed compound does release the active substance inside cancer cells thereby providing a relatively high Dox concentration in nuclei and a relevant cytotoxic effect. In contrast, we have also synthesized a similar conjugate with a stable amide linker and it did not release the drug at all. This compound was predominantly accumulated in cytoplasm and did not cause cell death. Preliminary in vivo evaluation has showed good efficiency for the degradable conjugate against PC3-PIP(PSMA+)-containing xenograft mine. Thus, we have demonstrated that the conjugate can be used as a template to design novel analogues with improved targeting, anticancer activity and lower rate of potential side effects. 3D molecular docking study has also been performed to elucidate the underlying mechanism of binding and to further optimization of the linker area for improving the target affinity. 相似文献