小分子自组装纳米递药系统研究进展

生物纳米技术在药物递送领域的应用为高端创新制剂的研发注入了新动力,一系列新型纳米递药系统被相继开发乃至应用于临床。其中,由小分子药物或前药自组装形成的纳米递药系统因具有制备工艺简便、载药量超高和易于实现工业化生产等优势而备受关注,已成为纳米递药系统领域的一个重要分支。本文总结了小分子自组装纳米递药系统的最新研究进展。首先,对小分子前药自组装纳米递药系统进行介绍,包括两亲性、疏水性和二聚体小分子前药自组装纳米递药系统。其次,分别介绍小分子化学药物和小分子生物药物自组装纳米递药系统的最新进展。再者,对小分子杂化共组装纳米递药系统进行总结和分析,包括小分子纯药共组装纳米递药系统、小分子前药共组装纳米递药系统及小分子前药/小分子纯药共组装纳米递药系统。最后,讨论了小分子自组装纳米递药系统的合理设计、应用前景和临床挑战,以期为新一代纳米制剂的设计与构建提供参考。     

钙离子对海藻酸钠自组装行为影响的AFM研究

利用氯化钙试剂掺入海藻酸钠溶液中诱导分子链聚集形成自组装膜，研究钙离子对海藻酸钠自组装膜结构的影响。运用原子力显微镜(Atomic force microscope，AFM)对不同浓度海藻酸钠在钙离子作用下的自组装膜进行成像，并结合红外谱图分析。当海藻酸钠浓度在0．01mg／m1和0．1mg／m1时，5m／m1 Ca^2 能很好的诱导海藻酸钠自组装膜，这种自组装结构呈现出典型的“蛋盒结构”。无机小分子通过与同种大分子的表面活性基团相互作用可以诱导高分子物质的自组装，这种自组装结构是一种非平衡状态下的耗散结构，自组装结构受高分子本身的性质与浓度、加入的小分子试剂的浓度、基片的性质以及外界温度等因素的影响。     

钙离子诱导硫酸软骨素自组装的AFM研究

利用Ca^2 试剂掺入硫酸软骨素（Chondroitin Sulfate，CS）溶液中诱导分子链在云母表面聚集形成自组装膜，用原子力显微镜（Atomic Force Microscope，AFM）在不同的时间段研究Ca^2 试剂对硫酸软骨素自组装膜结构的影响。结果表明当CS浓度为1.2mg/ml时，Ca^2 能很好的诱导CS自组装膜的形成，这种自组装结构会随时间发生形态学改变，具有不稳定性。说明了无机小分子通过与同种大分子的表面活性基团相互作用可以诱导高分子物质的自组装，这种自组装结构是一种非平衡状态下的耗散结构。     

原位自组装多肽在肿瘤和细菌感染诊断及治疗中的研究进展

摘要： 肿瘤和细菌感染严重危害人类健康， 因此亟需开发有效的诊疗方法以克服这两类疾病。原位自组装多肽能够特异识别病灶部位某些特异性高表达的物质， 靶向性地在病灶部位聚集， 并通过自组装形成稳定的纳米结构，从而实现疾病的精确诊断和有效治疗， 并降低对正常组织的毒副作用， 是一种在疾病诊疗方面应用前景广阔的医用材料。本文就原位自组装多肽在肿瘤和细菌感染的诊断及治疗中的研究进展进行综述。     

合成多肽药物质量控制研究探讨

合成多肽药物作为一种介于小分子和生物制品之间的特殊药物形式，既有小分子药物稳定性好和纯度高的特点，又具有生物药物生物活性高和毒副作用低的优势，越来越受到制药行业的关注。多肽是由多个氨基酸通过酰胺键共价连接而成，由于氨基酸异构和侧链修饰导致多肽药物与生物制品一样存在异质性的特点，而化学合成工艺复杂多样，杂质谱的鉴定相比小分子药物更为困难。因此合成多肽药物的质量控制既要满足化学合成药物的质量控制要求，又要兼顾生物制品的特点，对于制药行业存在很大挑战。文章结合国内外合成多肽药物药学研究的相关指导原则及研究进展，从多肽的鉴别、含量测定、杂质谱分析等方面出发，对合成多肽药物的质量控制进行全面的探讨和分析，以期为后续合成多肽类药物的质量控制研究提供参考。     

多肽的电泳分离

目的：对4种PAGE方法进行比较，选择出适用于分离小分子质量多肽的电泳方法。方法：用常规SDS-PAGE、低分子质量Tricine-SDS-PAGE、多肽SDS-PAGE以及含尿素的多肽SDS-PAGE4种方法对相同的样品进行电泳分离，并对分离效果进行比较。结果：常规SDS-PAGE不适合分离小分子质量多肽，Tricine-SDS-PAGE对分子质量小于10ku的样品效果不佳。多肽SDS-PAGE能分离分子质量在5～20ku的多肽，含尿素的多肽SDS-PAGE对分子质量小于5．0ku的多肽也能很好的分离。结论：含尿素的多肽SDS-PAGE对小分子质量多肽的分离效果最好，可根据实验的需要选择适合的电泳方式。     

小分子多肽类佐剂最新研究进展

免疫佐剂是指与抗原一起或先于抗原注入机体后,可增强机体对该抗原的免疫应答能力或改变免疫应答类型的辅助物质。最近发现,某些氨基酸残基数小于50的小分子多肽具有增强机体免疫活性的能力。这些小分子多肽类佐剂因其安全性好、生物相容性好、易合成、纯度高、制备成本低等优点逐渐引起人们的关注。此文综述了小分子多肽类佐剂疫苗的研究现状,并对小分子多肽类佐剂的发展未来作了展望。     

抗肿瘤多肽药物的作用机制及研究进展

肿瘤是世界医学的难题,寻找高效、低毒、易得的抗肿瘤药物迫在眉睫。在众多种类的抗肿瘤药物中,小分子多肽类药物以其分子量小、靶向性强、活性高、毒性弱、易于穿膜吸收等特点在抗肿瘤的实验研究及临床应用中得到广泛关注。小分子多肽具有抗肿瘤机制的多样性和合成的准确性及便利性,其不同功能片段可被融合使用,以增强其作用的靶向性、高效性。本文从多肽药物的不同抗肿瘤机制入手,分别对促凋亡多肽、免疫疗法多肽以及融合多肽抗肿瘤作用机制和活性研究做了简要概述,为多肽靶向、高效抗肿瘤研究提供新的思路。     

重组人生长激素稳定性研究进展

随着生物技术的发展,多肽类药物在临床上的应用越来越广泛,相应的制剂学研究也日益受到重视。与传统小分子有机药物相比,多肽具有稳定性差、体内半衰期短和生物膜透过性差等特点。     

蝮蛇毒小分子多肽的分离、纯化及其抗肿瘤作用研究

目的从长白山岩栖蝮蛇蛇毒中分离纯化1种小分子多肽Saxis,测定理化性质,研究其对肿瘤细胞的生长抑制作用。方法利用有机溶剂沉淀和Sephadex G-50S、ephadex G-25凝胶过滤色谱等方法分离纯化长白山栖岩蝮蛇蛇毒中的1种小分子多肽Saxis;采用Tricine-SDS-PAGE鉴定;利用Bradford蛋白质测定法测定蛋白质浓度;运用MTT比色法检测该小分子多肽对宫颈癌细胞Hela、肝癌细胞SMMC-7721和胃腺癌细胞SGC-7901的生长抑制作用。结果该小分子多肽Saxis的相对分子质量约为5 200,它能抑制Hela、SMMC-7721和SGC-7901细胞的增殖,并且对这3种肿瘤细胞的抗增殖作用具有药物剂量依赖关系,24 h的IC50分别为66.3,54.5,62.2μg/mL。结论利用有机溶剂沉淀和凝胶过滤色谱法可以从长白山岩栖蝮蛇蛇毒中分离纯化1种小分子多肽Saxis,其对多种肿瘤细胞的生长有抑制作用。     

Peptides and peptidomimetics in medicine, surgery and biotechnology

Despite the fact that they have been used for a century to treat several kinds of diseases, peptides and short proteins are now considered the new generation of biologically active tools. Indeed, recent findings suggest a wide range of novel applications in medicine, biotechnology, and surgery. The efficacy of native peptides has been greatly enhanced by introducing structural modifications in the original sequences, giving rise to the class of peptidomimetics. This review gives an overview of both classical applications and promising new categories of biologically active peptides and analogs. Besides the new entries in well known peptide families, such as antibiotic macrocyclic peptides, integrin inhibitors, as well as immunoactive, anticancer, neuromodulator, opioid, and hormone peptides, a number of novel applications have been recently reported. Outstanding examples include peptide-derived semi-synthetic vaccines, drug delivery systems, radiolabeled peptides, self-assembling peptides, which can serve as biomaterials in tissue engineering for creating cartilage, blood vessels, and other tissues, or as substrates for neurite outgrowth and synapse formation, immobilized peptides, and proteins. Finally, peptide-based biomaterials can find applications in bio-nanotechnology for bio-microchips, peptide nanorods and nanotubes, bio-sensors, bio-electronic devices, and peptide-metal wires.     

Self-assembling peptides: implications for patenting in drug delivery and tissue engineering

In this paper, a comprehensive review of recent patents concerning the molecular self-assembly of peptides, peptide amphiphiles and peptidomimetics into molecules through nanoarchitectures to hydrogels is provided. Their potential applications in the field of drug delivery and tissue engineering have been highlighted. The design rules of this rapidly growing field are centered mainly on the construction of peptides in the form of peptide amphiphiles, aromatic short peptide derivatives, all-amino acid peptide amphiphiles, lipidated peptides with single and multiple alkyl chains and peptide-based block copolymers and polymer peptide conjugates. The interest in patenting of self-assembling peptides is also driven by their type (I, II, III and IV) and their ability to form well-regulated highly-ordered structures such as β-sheets/β-hairpins, α-helices/coiled coils and to hierarchically self-organize into supra-molecular structures. The applicability of these systems in cell culture scaffolds for tissue engineering, drug and gene delivery and as templates for nanofabrication and biomineralization has inspired various groups over the globe. This resulted in development of self-assembling peptides as synthetic replacements of biological tissues, designing materials for specific medical applications, and materials for new applications such as diagnostic technologies. Furthermore, biologically derived and commercially available systems are also discussed herein along with a brief account of various awarded and pending patents in the past 10 years. An overview of the diversity of the patent applications is also provided for self-assembling systems based on nano- and/or micro-scale such as fibers, fibrils, gels, hydrogels, vesicles, particles, micelles, bilayers and scaffolds.     

Electrospun materials as potential platforms for bone tissue engineering

Nanofibrous materials produced by electrospinning processes have attracted considerable interest in tissue regeneration, including bone reconstruction. A range of novel materials and processing tools have been developed to mimic the native bone extracellular matrix for potential applications as tissue engineering scaffolds and ultimately to restore degenerated functions of the bone. Degradable polymers, bioactive inorganics and their nanocomposites/hybrids nanofibers with suitable mechanical properties and bone bioactivity for osteoblasts and progenitor/stem cells have been produced. The surface functionalization with apatite minerals and proteins/peptides as well as drug encapsulation within the nanofibers is a promising strategy for achieving therapeutic functions with nanofibrous materials. Recent attempts to endow a 3D scaffolding technique to the electrospinning regime have shown some promise for engineering 3D tissue constructs. With the improvement in knowledge and techniques of bone-targeted nanofibrous matrices, bone tissue engineering is expected to be realized in the near future.     

Protein- and peptide-based electrospun nanofibers in medical biomaterials

Electrospun fibers are being studied and developed because they hold considerable promise for realizing some advantages of nanostructured materials. The fibers can be made of biocompatible and biodegradable polymers. Electrospinning has therefore attracted interest in biotechnology and medicine, and there has been rapid growth in this area in recent years. This review presents an introduction to polymer nanofiber electrospinning, focusing on the use of natural proteins and synthetic peptides. We summarize key physical properties of protein-based and peptide-based nanofiber mats, survey biomedical applications of these materials, identify key challenges, and outline future prospects for development of the technology for tissue engineering, drug delivery, wound healing, and biosensors.From the Clinical EditorThis review focuses on polymer nanofiber electrospinning using natural proteins and synthetic peptides. The authors describe key properties and applications of these materials, and outline future prospects for tissue engineering, drug delivery, wound healing, and biosensors based on these nanomats and nanofibers.     

多肽抗生素研究进展

多肽抗生素是生物界中广泛存在的一类生物活性小肽 ,一般具有抗细菌或真菌的作用 ,有些还具有抗原虫、病毒或癌细胞的功能。按照化学结构的不同 ,多肽抗生素可分为5类 :①具有螺旋结构的线性多肽 ;②富含某种氨基酸的线性多肽 ;③含有一个二硫键的多肽 ;④含有两个或两个以上二硫键的多肽 ;⑤羊毛硫抗生素。根据作用机理的不同 ,多肽抗生素又可分为裂解细胞膜的裂解肽和非裂解肽。多肽抗生素已经开始用于医药、食品和植物抗病基因工程等方面 ,并且有着很大的发展潜力。     

Design of peptide-based vaccines for cancer

The immune system responds efficiently to bacteria, viruses and other agents however, the immune response to cancers is not as effective. In most cases other than specific genetic rearrangements leading to non-self proteins such as in leukemia and idiotypes in lymphoma, tumor associated proteins are self proteins and are not recognized by the immune system to prevent malignancy. In most cancers, patients develop antibodies and/or CTL-precursors to tumor associated antigens but are not effective in generating a therapeutic immune response. Adjuvants have been used with either whole tumors, subunits or peptides with the aim of increasing their immunity. Whole tumor antigens have certain advantages associated with it, such as ready availability as recombinant proteins, potential epitopes that can be presented by a number of MHC class I/II alleles and antibody development. The methods of identification of CD8 and CD4 epitopes either by use of epitope prediction algorithms or use of transgenic mice has made the use of defined synthetic peptides more attractive. The possibility to synthesize long peptides and introduce multiple epitopes (CD4 or CD8) from single or multiple antigens makes peptide a viable alternative to whole proteins. As an alternative to totally synthetic peptide constructs or polymers, polytopes have been generated by genetic engineering methods. In addition, to deliver immunogens to and to activate DC, receptor-mediated delivery of peptides using antibodies, cytokines and carbohydrates have been used. This review will encompass the various strategies, preclinical and clinical applications in designing peptide-based vaccines for cancer.     

抗菌肽研究进展

文章归纳并讨论了抗菌肽的来源及分类、作用及其分子机制、应用领域、基因表达策略和应用前景等。     

Antibodies and peptides in cancer therapy

Antibodies and peptides play a variety of roles in cancer therapy: monoclonal antibodies (mAbs) and peptides are directly used in anticancer therapy and also as targeting moieties. More than 10 mAbs, either unconjugated or in immunoconjugate forms have been approved for use in oncology. Various peptides, tumor necrosis factors (TNFs), and cell surface-targeted peptides have been identified using phage-display libraries. In combination with standard chemotherapeutic agents, mAbs and peptides can significantly increase the toxicity of anticancer drugs to tumors and reduce their adverse side effects on normal tissues. The present review summarizes some major applications of antibodies and peptides in cancer therapy.     

Endotoxin neutralizing peptides

Neutralization and sequestration of bacterial lipopolysaccharide which plays a key role in gram-negative sepsis is required to block the progression of sepsis at early stages in addition to destroying bacteria. Many of the host defense peptides which have antimicrobial activity are also able to bind to and neutralize LPS, however, these two activities do not necessarily correlate. Due to its toxicity application of polymyxin B as the prototype of LPS neutralizing peptide is limited to topical applications and extracorporeal removal of endotoxin. Development of novel endotoxin neutralizing peptides without the toxicity of polymyxin B have been based on the natural host defense peptides, fragments of LPS binding proteins and engineered peptides. Neutralization of LPS can be achieved through several different peptide fold motifs, which are reviewed in this article. Endogenous host defense peptides, fragments of endotoxin-binding proteins and synthetic anti-endotoxin peptides fold into alpha-helical, beta-hairpin, extended and compact conformations without regular secondary structure. In animal models many of the peptides have demonstrated good in vitro and in vivo endotoxin neutralizing activity but up to now none of the peptides has been approved for clinical application with an anti-endotoxin indication. Recent developments include preparation of novel types of endotoxin neutralizing compounds such as peptides modified by lipophilic moieties and non-peptidic molecules, particularly lipopolyamines and on the other hand additional medical applications such as extracorporeal endotoxin removal, targeting to inflammation sites or endotoxoid based vaccines.     

Coacervate delivery systems for proteins and small molecule drugs

Coacervates represent an exciting new class of drug delivery vehicles, developed in the past decade as carriers of small molecule drugs and proteins. This review summarizes several well-described coacervate systems, including: i) elastin-like peptides for delivery of anticancer therapeutics; ii) heparin-based coacervates with synthetic polycations for controlled growth factor delivery; iii) carboxymethyl chitosan aggregates for oral drug delivery; iv) Mussel adhesive protein and hyaluronic acid coacervates. Coacervates present advantages in their simple assembly and easy incorporation into tissue engineering scaffolds or as adjuncts to cell therapies. They are also amenable to functionalization such as for targeting or for enhancing the bioactivity of their cargo. These new drug carriers are anticipated to have broad applications and noteworthy impact in the near future.