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。     

温敏聚合物自组装纳米粒子在抗肿瘤药物递送中的应用

作为抗肿瘤治疗的主要手段,化疗最大的缺陷在于化疗药物缺乏肿瘤靶向性,易对正常组织产生高毒性,并导致治疗效果不理想。为了解决这一问题,越来越多的聚合物纳米载体被用于递送抗肿瘤药物,包括对温度刺激能作出响应的温敏聚合物自组装纳米载体。笔者综述了近年来温敏聚合物自组装载体及其纳米粒子的研究进展,并介绍了其在抗肿瘤药物递送中的应用。     

酸敏感响应型纳米药物递送系统在肿瘤治疗中应用的研究进展

癌症是危害人类生命健康的一类重大疾病。肿瘤组织与正常组织相比具有特殊的酸性微环境,利用此特殊性质,研究者设计了一系列具有酸敏感响应性的药物递送载体,用以增强抗肿瘤药物在肿瘤部位的富集、肿瘤组织的渗透和肿瘤细胞的摄取,同时加速药物在靶部位的释放,从而提高肿瘤治疗的效果。本文综述了响应于肿瘤微酸环境的纳米药物递送系统的设计及其在抗肿瘤治疗中的应用。     

壳聚糖与葡聚糖在基因递送应用中的研究进展

在基因疗法中,天然高分子多聚糖因其高生物相容性和可修饰性而成为良好的基因递送材料。壳聚糖和葡聚糖是2种重要的天然高分子多聚糖,它们本身及其衍生物都可以用做基因药物载体材料。研究者采用多种方法对壳聚糖和葡聚糖进行改良,拓宽它们在基因递送中的应用范围。本综述介绍了两者的结构和性质特点以及近年来两者及其衍生物在基因递送应用中的研究进展,最后对它们的发展前景进行了展望。     

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。     

碳点复合聚多巴胺载药体系用于肿瘤协同治疗的评价

目的 为了提高药物的治疗效果,降低毒性和不良反应,研究制备了一种基于碳点(CDs)修饰的聚多巴胺(polydopamine, PDA)的特异性药物递送系统。方法 采用水热法制备直径约为4 nm的CDs,然后制备碳点复合聚多巴胺(PDA@CDs)载体。以盐酸阿霉素(DOX)作为模型药物,制备DOX/PDA@CDs载药体系。采用透射电子显微镜、Zeta电位、动态光散射和荧光光谱等对载药体系进行表征。模拟肿瘤微环境以及NIR光照射对载药体系进行体外释放的考察,采用细胞水平实验评价该体系的热疗和化疗协同治疗效果。结果 PDA@CDs载体具有优良的光热性能和光热稳定性。体外释放曲线表明,在pH 7.4 PBS和无近红外光照射的情况下,DOX释放量较少,在高过氧化氢浓度、pH 5.0 PBS和近红外光照射下,DOX的释放显著增加。细胞摄取实验证明PDA@CDs能被细胞摄取,且可以发射绿色荧光。细胞毒实验表明,DOX/PDA@CDs在NIR光照后显示出优异的化疗/热疗协同杀伤肿瘤细胞的作用。结论 DOX/PDA@CDs具有pH/H₂O₂/NIR多重响应性释...     

酵母微囊作为口服药物递送载体的研究进展

酵母微囊是一种表面粗糙多孔、核心中空的天然药物递送载体，具有良好的安全性和高靶向性、高稳定性，在口服药物递送系统中具有极佳的应用前景。酵母细胞经过酸碱和有机溶剂处理、洗涤后可获得疏松多孔的酵母微囊，后者可借助静电相互作用、被动扩散、疏水作用等方式包载药物。酵母微囊表面主要由β-葡聚糖组成，可在胃肠环境中保持稳定，可被免疫细胞表面相关受体识别，从而激活免疫反应，并可在被摄取后随淋巴细胞的运动将所载药物运送至病变部位。酵母微囊安全性高，非常适合递送疫苗、抗炎药物及抗肿瘤药物，其不仅可实现上述药物的口服递送，而且能增强药物效果，提高药物的靶向性。今后可开展更多全身转运机制的相关研究或开发更加高效的联合给药系统，以充分发挥酵母微囊的临床价值。     

细胞膜仿生纳米技术在肿瘤靶向递药系统中的研究进展

纳米技术的发展为构建安全高效、精准可控的药物递送系统(drug delivery system, DDS)提供了可能。其中,有机或无机合成纳米载体已被广泛报道并用于肿瘤治疗药物的递送,但部分载体存在易被机体内免疫系统清除、制备过程繁琐和体内安全性较差等问题。近年来,随着生物医学的发展,基于仿生技术的生物膜介导的纳米药物递送系统,因其有机整合了天然生物膜的低免疫原性、肿瘤靶向性和智能纳米载体设计的可调控性、多功能性,有望实现纳米技术在肿瘤靶向治疗上的新突破。本文基于细胞膜仿生技术和纳米医学在肿瘤治疗领域的最新进展,从细胞膜仿生纳米技术的实验基础、膜仿生纳米递药平台的分类和在肿瘤靶向治疗上的应用三方面进行阐述,旨在为仿生智能DDS的设计及其在肿瘤靶向治疗中的发展提供参考。     

纳米材料和纳米药物递释系统在抗细菌感染中的应用及机制

细菌感染治疗是全球关注的医学问题,抗菌药物的误用和过度使用,病原体新耐药机制的出现,导致抗菌药物的耐药性问题日益严峻,持续威胁抗感染治疗效果,并增加疾病传播、严重疾病的死亡风险。随着生物材料和纳米技术广泛应用于生物医药,围绕抗细菌感染展开了广泛研究。纳米无机材料特殊的光电磁和高穿透性等物理化学性质可产生天然抗菌作用。纳米药物递送系统可实现药物缓控释,靶向输送从而提高抗菌疗效。本综述对抗菌药物的耐药机制进行阐述,并对围绕纳米材料、纳米药物系统包括脂质体、聚合物纳米粒、树枝状聚合物、仿生纳米载体等开展的抗细菌感染研究进行总结。纳米材料和纳米技术为提高抗细菌感染疗效,并可能克服耐药性的新型制剂的研发提供了有希望的策略。     

基于D-α维生素E聚乙二醇琥珀酸酯的纳米载体在皮肤疾病治疗中的研究进展

皮肤相关疾病的发病率逐年增加，大部分皮肤疾病的治疗以外用制剂为主，但存在透皮率低、稳定性差等问题。D-α维生素E聚乙二醇琥珀酸酯(D-α-tocopherol polyethylene glycol succinate，TPGS)具有聚乙二醇与维生素E的双重功能，在药物递送系统中可作为增溶剂、促渗剂、乳化剂、稳定剂，用于提高药物的溶解度、稳定性、包封率、载药量及透皮吸收率等。本文对TPGS的理化性质、其作为药用辅料的应用、在纳米载体系统中的应用及基于TPGS的纳米载体在皮肤疾病治疗中的研究等进行综述，以期为开发治疗皮肤相关疾病的新型TPGS纳米载体提供参考。     

The role of biomimetism in developing nanostructured inorganic matrices for drug delivery

Background: Biomimetism of synthetic biomaterials can be carried out at different levels, such as composition, structure, morphology, bulk and surface chemical–physical properties. Biomaterials can be turned into biomimetic imprinting of all these characteristics in order not only to optimise their interaction with biological tissues, but also to mimic biogenic materials in their functionalities. Objective: This review outlines the biomimetic chemical–physical properties of inorganic matrices in controlling drug release. Methods: This review is restricted to phosphates and silica among inorganic biomaterials proposed as drug delivery vehicles. Conclusion: By mimicking nature, we can design and synthesise inorganic smart materials that are reactive towards biological tissues and can release bioactive molecules by a kinetic that is controlled not only by the matrix tailored chemical–physical properties, but also by the response to stimuli induced by physiological or pathological processes.     

Biodegradable ‘intelligent’ materials in response to chemical stimuli for biomedical applications

Background: Biodegradable stimuli-responsive materials, which exhibit large and sharp physical–chemical changes in response to small physical or chemical stimuli, are attracting increasing interests because of their potential applications in biomedical fields, such as transient implants, drug delivery carriers, and tissue engineering scaffolds. Our previous review (see page 493 of issue 4) summarized those biodegradable ‘intelligent’ materials that respond to physical stimuli, such as temperature, ultrasound, and magnetic field. Biodegradable ‘intelligent’ materials that could respond to chemical stimuli, such as pH and specific molecules, have also been studied intensively and significant progress in this field has been achieved. As a single stimulus-responsive property would limit practical application, multi-stimuli-responsive materials are receiving increasing interest and considerable attention. Objective/methods: This review summarizes the development of biodegradable ‘intelligent’ materials in response to chemical stimuli and to dual stimuli; their potential biomedical applications are also introduced. A detailed analysis of publications and patents on such materials in recent years is presented. Results/conclusion: Most of biodegradable stimuli-responsive materials are currently still at a developmental research stage. Further work is required to improve the responsive properties between the materials and the biological environments, so that the clinical applicability of such devices could be successful. We hope that our review will be helpful in the future development of new stimuli-responsive biodegradable polymers or polymeric systems that can be used reliably in real-life applications.     

Physicochemical and Mineralogical Characterization of Test Materials used in 28-Day and 90-Day Intratracheal Instillation Toxicology Studies in Rats

Two recent intratracheal instillation toxicology studies in rats clearly show that a naturally occurring quartz, with occluded crystal surfaces (quartz isolate), produced significantly less inflammatory response than a crushed reference quartz (DQ12). Respirable-size quartz isolate was isolated from bentonite parent rock, without crushing or the use of chemicals, to ensure that the surface properties of the quartz particles were unaltered. The isolation technique utilized gentle mechanical dispersion followed by sedimentation in an aqueous medium. Extensive mineralogical and chemical characterizations were undertaken to define the physicochemical properties of the test materials. The characterizations showed significant, measurable physicochemical differences between the two quartz types. These differences may help to explain the difference in toxicological response associated with these materials. The evaluation methods and resulting data that characterized the chemical and physical properties of the instillation test materials are discussed. The data presented show that such characterizations are essential if meaningful correlations are to be made between test materials and their toxicological profiles.     

Physicochemical and mineralogical characterization of test materials used in 28-day and 90-day intratracheal instillation toxicology studies in rats

Two recent intratracheal instillation toxicology studies in rats clearly show that a naturally occurring quartz, with occluded crystal surfaces (quartz isolate), produced significantly less inflammatory response than a crushed reference quartz (DQ12). Respirable-size quartz isolate was isolated from bentonite parent rock, without crushing or the use of chemicals, to ensure that the surface properties of the quartz particles were unaltered. The isolation technique utilized gentle mechanical dispersion followed by sedimentation in an aqueous medium. Extensive mineralogical and chemical characterizations were undertaken to define the physicochemical properties of the test materials. The characterizations showed significant, measurable physicochemical differences between the two quartz types. These differences may help to explain the difference in toxicological response associated with these materials. The evaluation methods and resulting data that characterized the chemical and physical properties of the instillation test materials are discussed. The data presented show that such characterizations are essential if meaningful correlations are to be made between test materials and their toxicological profiles.     

海洋来源的可生物降解材料

摘要:近年来,可生物降解材料在生物医学领域的研究取得了突破进展。来源于海洋的可生物降解材料有很好的生物相容性和多样的生物活性,可作为药物的缓控释载体,在组织工程学中可以作为组织替代物和多孔支架,应用十分广泛。本文着重介绍了多糖和蛋白质两大类海洋来源可生物降解材料的物理、化学、生物特性和降解性能,总结了它们在生物医学领域的应用。     

Biodegradable ‘intelligent’ materials in response to physical stimuli for biomedical applications

Background: Stimuli-responsive materials that undergo dramatic changes in physical–chemical properties in response to mild physical changes in environmental conditions are attracting increasing interest because of their potential application in biomedical fields. Biodegradable materials are highly desired for most biomedical applications in vivo, such as transient implants, drug-delivery carriers, and tissue engineering scaffolds. Biomedical systems that are both biodegradable and stimuli-responsive have therefore been studied intensively and significant progress in this field has been achieved. Objective/methods: This review summarizes the development of biodegradable ‘intelligent’ materials in response to physical stimuli and their potential biomedical applications. A detailed analysis of publications and patents on such materials in recent years is presented. Results/conclusion: Although biodegradable stimuli-responsive materials are highly attractive for biomedical applications, most such materials are currently at a developmental research stage. Additionally, single stimulus-responsive property limits the practical applications of these materials. To achieve more favorable applications for these materials, further efforts are still necessary, especially for developing multi-stimuli-responsive functions of materials and improving the stimuli-responsive properties of such materials in a biological environment. Bearing in mind the great prospect of these biodegradable stimuli-responsive materials, we hope that this review will help in the future development of stimuli-responsive polymers or systems that could be reliably employed in biomedical applications.     

辛伐他汀组织工程骨材料的制备及性能研究

目的:探讨制备的辛伐他汀组织工程骨复合支架材料的理化性质及力学强度.方法:将同种异体骨、Ⅰ型胶原、辛伐他汀进行系列理化处理,制备成单纯组织工程骨材料、胶原组织工程骨材料、辛伐他汀组织工程骨复合材料.制备后的材料用扫描电镜观察其形貌特征,用X线衍射分析材料成分,并对材料的力学性能进行分析测定.结果:单纯组织工程骨材料具有天然骨的网状孔隙系统;胶原组织工程骨材料具有天然骨的网状孔隙系统,微孔表面覆盖胶原膜;辛伐他汀组织工程骨复合材料具有骨组织的天然网状孔隙系统,微孔表面可见胶原膜覆盖;单纯组织工程骨材料、胶原组织工程骨材料、辛伐他汀组织工程骨复合材料主要成分均为羟基磷灰石[HA,Ca10(OH)2(PO4)6],3种材料的孔径大小、空隙率、弯曲强度和压缩强度差异无统计学意义(P＞0.05).结论:辛伐他汀组织工程骨复合材料与其他2种材料理化性质和力学强度相同,可作为一种有效的天然组织工程骨支架材料.     

Nanoparticles for detection and diagnosis

Nanoparticle based platforms for identification of chemical and biological agents offer substantial benefits to biomedical and environmental science. These platforms benefit from the availability of a wide variety of core materials as well as the unique physical and chemical properties of these nanoscale materials. This review surveys some of the emerging approaches in the field of nanoparticle based detection systems, highlighting the nanoparticle based screening methods for metal ions, proteins, nucleic acids, and biologically relevant small molecules.     

聚氨基酯作为基因载体的研究进展

随着基因治疗研究的不断深入,寻求一种高效、安全、靶向表达的载体已成为了基因治疗的核心问题之一。聚氨基酯(poly amino ester,PAE)作为一种新型的阳离子聚合物基因载体,具有原料廉价、合成简单、结构多样、可降解、细胞毒性低和转染效率高等优点,已越来越受到人们的关注。本文将从聚氨基酯的合成途径、理化性质、聚氨基酯/DNA纳米粒的制备及聚氨基酯/DNA纳米粒转染效率和影响因素等方面详细阐述了近年来聚氨基酯作为基因载体的研究进展。     

Potential applications of boron nitride nanotubes as drug delivery systems

In recent years, there has been an explosion of research in the ‘bio-nano’ field, with the discovery and introduction of ever more fascinating materials for applications as drug delivery systems, sensors, transducers, and so on. The author's group, for the first time in the literature, proposed boron nitride nanotubes as a valid alternative to carbon nanotubes and other kinds of inorganic materials, because of their improved chemical properties that theoretically guarantee better stability and compatibility in a biological context. In this paper, the bio-applications of boron nitride nanotubes that have emerged in the literature are summarized, with special attention given to their exploitation as safe drug delivery and targeting carriers. Finally, the possibility of combining their physical and chemical properties is approached, highlighting the features that render these innovative nanovectors unique and exceptional candidates for many bio-applications.