柠檬酸递送药物的研究进展

柠檬酸因价廉易得,具有良好的生物相容性、生物可降解性和多功能性受到了广泛关注,已经发展出了众多的柠檬酸基生物材料,并在药物递送系统取得实际进展。总结了柠檬酸在递送基因治疗药物、蛋白质治疗药物、免疫治疗药物、化学治疗药物中的研究进展,希望柠檬酸在药物递送系统得到进一步的研究发展。     

抗肿瘤多药联用型纳米递送系统的研究进展

由于肿瘤病理复杂性,临床治疗中对于多种药物联合使用的需求日益迫切。多药联用可同时作用于多通路和多靶点发挥协同增效作用,然而目前临床多药联用的递送策略仍有较大优化空间。纳米药物递送系统可精准调控药物多组分灵活荷载,并携载药物克服生理、病理屏障,实现肿瘤组织、细胞的有效富集,完成持续、可控和靶向递送,实现抗肿瘤增效减毒,已在肿瘤多药联合治疗领域展现出广阔的前景,并成为药物研发的新方向之一。本文对近年来肿瘤联合用药治疗策略及其递送系统的研究进展进行了综述,并分析和探讨了多药联用型纳米递送系统的应用瓶颈、现有研究面临的挑战及未来的发展趋势。     

肿瘤微环境响应型的RNA药物递送系统的研究进展

肿瘤作为全球危害人类健康的重大疾病之一,亟需寻找更加安全高效的治疗方案。核糖核酸(ribonucleic acid, RNA)药物的基因疗法可以调节肿瘤相关基因的表达,已在临床前和临床试验中展示出良好的抗肿瘤治疗潜力。基于肿瘤组织在pH、特异性酶浓度或氧化还原梯度变化等微环境信号特征与正常组织存在差异性,各类微环境响应型纳米载体正在被研究开发用于递送RNA药物,实现对肿瘤组织与细胞的靶向递送,提高RNA药物的抗肿瘤疗效并且降低不良反应。本文综述了肿瘤微环境的病生理特征以及各类肿瘤微环境响应型载体策略,旨在为设计安全高效的RNA药物肿瘤靶向递送系统提供参考。     

壳聚糖纳米粒作为药物递送系统在癌症治疗中的应用

癌症是威胁人类生存的恶性疾病之一。近年来,利用纳米技术将药物靶向递送到肿瘤部位,可以增加疗效并降低毒性,为癌症治疗带来了新希望。壳聚糖是自然界唯一存在的碱性多糖,具有良好的生物相容性和生物可降解性。此外,其反应位点多,可制成不同性质的衍生物,广泛用于药物递送系统和组织工程支架,在生物医药领域具有重要的应用价值。本综述对近年来壳聚糖纳米粒在抗癌药物递送方面的研究进展进行介绍,重点介绍了壳聚糖纳米粒的制备、被动靶向、主动靶向和刺激-响应药物递送系统方面的研究进展。     

红细胞作为药物递送系统的研究进展

传统的治疗药物存在稳定性差、摄取效率低、细胞毒性大以及靶向能力差等缺点。因此需要安全的药物传递系统来延长药物在体内的循环和暴露。以红细胞为载体的新型药物递送系统凭借其良好的生物相容性、低免疫原性以及长循环时间而逐渐成为理想的药物递送平台。基于红细胞的药物递送系统包括多种类型,主要有红细胞膜包裹纳米颗粒载药系统和基因工程红细胞等。另外,对红细胞进行功能化修饰,可显著增强靶向性,进一步开发和扩大红细胞载药体系在多种疾病治疗中的应用。本研究介绍了以红细胞为载体的化学药物及疫苗的递送方法,重点讨论了仿生纳米红细胞药物递送系统及其对机体各部位的靶向性研究,并且总结了近年来基因工程红细胞策略的研究进展。     

基于组氨酸的肿瘤靶向药物递送系统研究进展

组氨酸作为一种碱性氨基酸, pK_a接近肿瘤弱酸微环境pH,其带电性和溶解性具有pH敏感性,在中性环境中,组氨酸不带电,表现为疏水特性,而在肿瘤酸性环境中,组氨酸可质子化带正电,同时转变为亲水特性,因此,组氨酸被广泛应用于靶向肿瘤弱酸性微环境的药物递送系统设计。本文全面综述了近年来基于组氨酸构建肿瘤靶向药物递送系统的研究进展,系统总结了利用组氨酸促进细胞摄取和调控药物释放的设计思路,并指出了相关研究工作的共性问题和未来发展方向。     

基于外泌体的抗肿瘤药物靶向递送的研究进展

外泌体是生命体内细胞进行信息传递的重要方式之一,主要的生理病理过程均离不开外泌体的参与,包括细胞耐药、感染传播、肿瘤发展和心血管疾病等。外泌体的生物学职能使其天然具有免疫原性低、递送效率高、可跨过多种生物屏障和具有靶向性等特点,这些优点也促使人们尝试将其用作药物递送载体,以克服一些药物稳定性差、溶解度低、生物利用度不足和毒性较高的缺点。本文介绍了外泌体在抗肿瘤药物递送方面的最新研究进展,包括小分子化疗药物、生物大分子和核酸类药物的递送,还讨论了外泌体的提取、载药及改造方法,并对其应用前景进行了展望。     

抗肿瘤药物靶向递送系统专刊评述

如果把原料药比作炸药,药物递送系统则像是大炮,可把炸药输送到靶标。杀伤力越大的炸药就越是需要精准输送,这就不难理解为什么抗肿瘤化疗药物特别需要靶向递送。理想的靶向递送系统可有效载带药物,克服生理病理屏障,实现靶组织/细胞的高效富集,发挥增效减毒的功效,在肿瘤治疗领域具有广阔应用前景,是递送系统研发的重要方向。     

生物大分子药物无创眼内递送研究进展

生物大分子药物为许多眼科疾病患者带来了重见光明的希望,但由于眼部存在各种动态及静态吸收屏障,此类药物难以实现安全有效的眼内递送。临床上,生物大分子需通过眼内注射方式给药,而频繁的眼内注射伴随着诸多副作用,且患者顺应性差。构建理想的眼部药物递送系统,实现生物大分子的无创给药,尤其是将其递送至眼后段以治疗眼底疾病,始终是亟待满足的眼科需求。综述阻碍药物眼部吸收的各种生理屏障,以及近年来采用纳米递药系统、细胞穿膜肽及其他一些物理手段实现多肽蛋白类药物及基因药物眼内无创递送的研究进展,旨在为相关研究提供参考。     

基于聚多巴胺特性构建的肿瘤靶向药物递送系统的研究进展

聚多巴胺(polydopamine, PDA)是受到贻贝中黏附蛋白启发而合成的一种新型聚合物,其具有良好的生物相容性、优异的光热转换性能、黏附性与高化学反应性和多重药物释放响应机制等天然优势,在肿瘤靶向药物递送系统中得到了广泛的应用。本综述就近年来基于PDA构建的药物递送系统在肿瘤靶向中的应用进行了总结,以期为构建更合理、更有效的基于PDA的多功能协同肿瘤治疗平台提供参考。     

叶酸受体介导的靶向纳米给药系统研究进展

叶酸受体在许多恶性肿瘤细胞表面过度表达,而在正常细胞中则几乎不表达或只有少量表达。利用叶酸受体表达的特性,通过将叶酸修饰于药物载体表面,可使药物靶向输送至叶酸受体过度表达的肿瘤细胞中,从而避免对正常细胞产生毒性,提高药物疗效;而纳米给药系统因粒径较小等原因可使药物在肿瘤部位浓集。本文对近年来叶酸受体介导的靶向纳米给药系统进行了综述。     

Cell-mediated drug delivery

Introduction: Drug targeting to sites of tissue injury, tumor or infection with limited toxicity is the goal for successful pharmaceutics. Immunocytes (including mononuclear phagocytes (dendritic cells, monocytes and macrophages), neutrophils and lymphocytes) are highly mobile; they can migrate across impermeable barriers and release their drug cargo at sites of infection or tissue injury. Thus, immune cells can be exploited as Trojan horses for drug delivery.

Areas covered: This paper reviews how immunocytes laden with drugs can cross the blood–brain or blood–tumor barriers to facilitate treatments for infectious diseases, injury, cancer, or inflammatory diseases. The promises and perils of cell-mediated drug delivery are reviewed, with examples of how immunocytes can be harnessed to improve therapeutic end points.

Expert opinion: Using cells as delivery vehicles enables targeted drug transport and prolonged circulation times, along with reductions in cell and tissue toxicities. Such systems for drug carriage and targeted release represent a new disease-combating strategy being applied to a spectrum of human disorders. The design of nanocarriers for cell-mediated drug delivery may differ from those used for conventional drug delivery systems; nevertheless, engaging different defense mechanisms in drug delivery may open new perspectives for the active delivery of drugs.     

微透析技术在肿瘤药物研究中的应用进展

微透析技术具有连续动态微创取样优势,能实时在线研究正常生理和肿瘤病理情况下肿瘤药物在体内,尤其是肿瘤组织局部的分布、代谢和消除,利用PK/PD参数模型设计个体化给药方案,预防和减少肿瘤药物的毒性反应。同时,微透析技术还可以应用于肿瘤细胞外间质微环境中生化物质的监测以及肿瘤药物局部给药治疗,是肿瘤药物研究的重要技术手段。本文对近年来微透析在肿瘤药物研究中的应用进展进行检索和归纳,为微透析技术在取样、监测以及治疗领域的进一步研究应用提供参考。     

Application of hyaluronic acid as carriers in drug delivery

Hyaluronic acid has good biocompatibility, biodegradability, and nonimmunogenicity. In addition, it has the ability to recognize specific receptors that are overexpressed on the surface of tumor cells, and cancer drugs can be targeted to the tumor cells to better kill them. Therefore, hyaluronic acid has attracted much attention as drug delivery vehicle. Herein, the application of hyaluronic acid as carrier in drug delivery was analyzed and summarized in detail. It showed that hyaluronic acid would have broad prospects for drug delivery.     

纳米粒给药系统逆转肿瘤多药耐药性的研究进展

多药耐药是导致肿瘤化疗失败的主要原因。对于大多数抗肿瘤药物,肿瘤细胞均会产生多药耐药现象, 但其耐药机制,目前没有统一的看法。本文对纳米粒给药系统逆转肿瘤多药耐药性进行了综述, 包括3种载药系统: 非修饰的、配体修饰的和多功能纳米粒给药系统,并对纳米粒给药系统逆转肿瘤多药耐药性的机制进行探讨。纳米粒通过拮抗和抵消肿瘤细胞主动外排药物的作用,提高肿瘤细胞内的药物浓度,同时减小对正常细胞的毒副作用, 逆转肿瘤的多药耐药性。这种新型的给药系统,结合了纳米技术及主动和被动靶向给药策略,在癌症治疗方面已显示出巨大的应用前景。       

核素药物在肿瘤细胞治疗中的应用研究进展

目前,用于医学诊疗的核素种类繁多,在肿瘤细胞的诊断和治疗等方面都发挥着显著且有效的作用。由于肿瘤细胞的异质性和肿瘤微环境的高度可变性,使得提供精确诊断和靶向杀伤等功能的放射性核素偶联药物成为肿瘤精准医疗中不可或缺的手段和工具。结合近年来核素药物的临床前研究和临床试验,详细介绍诊断类核素在肿瘤细胞治疗中的应用,以及治疗类核素与其他肿瘤细胞疗法的协同治疗的应用,为核素药物的配对诊疗研究及临床转化提供发展方向。     

外泌体在胶质瘤治疗中的研究进展

胶质瘤是最常见的原发恶性脑肿瘤。传统化疗药物对胶质瘤靶向性差,且血脑屏障穿透性低,因而在胶质瘤治疗中的应用受到限制。外泌体作为新一代的递药载体,具有良好的生物相容性、稳定性和血脑屏障穿透性,近年来被广泛应用于脑部疾病的靶向递药研究,成果斐然。介绍了外泌体的结构和生物学特性,并对外泌体作为药物递送载体的脑靶向递送策略以及外泌体在胶质瘤治疗中的研究进展进行综述。     

Nano carriers for drug transport across the blood–brain barrier

Effective therapy lies in achieving a therapeutic amount of drug to the proper site in the body and then maintaining the desired drug concentration for a sufficient time interval to be clinically effective for treatment. The blood–brain barrier (BBB) hinders most drugs from entering the central nervous system (CNS) from the blood stream, leading to the difficulty of delivering drugs to the brain via the circulatory system for the treatment, diagnosis and prevention of brain diseases. Several brain drug delivery approaches have been developed, such as intracerebral and intracerebroventricular administration, intranasal delivery and blood-to-brain delivery, as a result of transient BBB disruption induced by biological, chemical or physical stimuli such as zonula occludens toxin, mannitol, magnetic heating and ultrasound, but these approaches showed disadvantages of being dangerous, high cost and unsuitability for most brain diseases and drugs. The strategy of vector-mediated blood-to-brain delivery, which involves improving BBB permeability of the drug–carrier conjugate, can minimize side effects, such as being submicrometre objects that behave as a whole unit in terms of their transport and properties, nanomaterials, are promising carrier vehicles for direct drug transport across the intact BBB as a result of their potential to enter the brain capillary endothelial cells by means of normal endocytosis and transcytosis due to their small size, as well as their possibility of being functionalized with multiple copies of the drug molecule of interest. This review provids a concise discussion of nano carriers for drug transport across the intact BBB, various forms of nanomaterials including inorganic/solid lipid/polymeric nanoparticles, nanoemulsions, quantum dots, nanogels, liposomes, micelles, dendrimers, polymersomes and exosomes are critically evaluated, their mechanisms for drug transport across the BBB are reviewed, and the future directions of this area are fully discussed.     

纳米医药技术在恶性肿瘤治疗中的应用

纳米药物具有靶向性和药物控释性的特点 ,与其他恶性肿瘤治疗方法相辅相承 ,并可在肿瘤组织的细胞和亚细胞水平上发挥作用 ,尤其是在转移性恶性肿瘤的治疗领域具有巨大的潜力。本文介绍纳米医药技术在恶性肿瘤治疗领域的研究和进展。     

Nanocarrier-mediated drugs targeting cancer stem cells: an emerging delivery approach

Introduction: Cancer stem cells (CSCs) play an important role in the development of drug resistance, metastasis and recurrence. Current conventional therapies do not commonly target CSCs. Nanocarrier-based delivery systems targeting cancer cells have entered a new era of treatment, where specific targeting to CSCs may offer superior outcomes to efficient cancer therapies.

Areas covered: This review discusses the involvement of CSCs in tumor progression and relevant mechanisms associated with CSCs resistance to conventional chemo- and radio-therapies. It highlights CSCs-targeted strategies that are either under evaluation or could be explored in the near future, with a focus on various nanocarrier-based delivery systems of drugs and nucleic acids to CSCs. Novel nanocarriers targeting CSCs are presented in a cancer-specific way to provide a current perspective on anti-CSCs therapeutics.

Expert opinion: The field of CSCs-targeted therapeutics is still emerging with a few small molecules and macromolecules currently proving efficacy in clinical trials. However considering the complexities of CSCs and existing delivery difficulties in conventional anticancer therapies, CSC-specific delivery systems would face tremendous technical and clinical challenges. Nanocarrier-based approaches have demonstrated significant potential in specific drug delivery and targeting; their success in CSCs-targeted drug delivery would not only significantly enhance anticancer treatment but also address current difficulties associated with cancer resistance, metastasis and recurrence.