Antineoplastic Drug-Free Anticancer Strategy Enabled by Host-Defense-Peptides-Mimicking Synthetic Polypeptides

An antineoplastic drug-free anticancer strategy enabled by host defense peptides (HDPs)-mimicking synthetic polypeptides is reported. The polypeptide exhibits a broad spectrum of anticancer activity in 12 cancer cell lines, including drug-resistant and highly metastatic tumor cells. Detailed mechanistic studies reveal that the cationic anticancer polypeptide (ACPP) can directly induce rapid necrosis of cancer cells within minutes through a membrane-lytic mechanism. Moreover, a pH-sensitive zwitterionic derivative of ACPP (DA-ACPP) is prepared for in vivo application. DA-ACPP shows negligible hemolysis under neutral physiological conditions, and can be converted back to ACPP in slightly acidic tumor environments, resulting in selective killing of cancer cells. Consequently, DA-ACPP shows an effective inhibition of tumor growth in both 4T1 orthotopic breast tumor models and B16-F10 melanoma pulmonary metastatic models. Overall, these findings demonstrate that synthetic HDPs-mimicking polypeptides represent safe and effective antineoplastic agents, which sheds new light on the development of drug-free synthetic polymers for cancer therapy.     

Promising antimicrobial agents designed from natural peptide templates

Treatment of infectious diseases is a paramount healthcare issue as the number of multidrug resistant pathogens rise rendering our aging small-molecule antibiotics ineffective. Innovation and discovery in new molecular species that are active against novel targets is vital to meet the challenges of resistance development. The ability of host-defense, or antimicrobial, peptides (AMPs) to selectively target the harmful microbial membrane over that of a host’s is a unique characteristic making these innate immune effectors promising candidates to fill the growing therapeutic void. Despite nearly two decades of active research into their selective mechanism against pathogens, few peptides have been found suitable for pharmaceutical applications. Fundamental structure–activity principles underlying the physiochemical properties of AMPs have guided the development and design of synthetic alternatives to peptide-based drugs. Here we first review work in understanding the mechanism and membrane selectivity of AMPs as it provides a good basis for the interpretation of other membrane-active agents as the same physical and chemical driving forces are at work. Recent advances in the rational design of synthetic mimics of antimicrobial peptides (SMAMPs) will also be discussed. Emphasis is placed on the paradigm shift that a rigid secondary structure is not required for the membrane-disruptive ability of SMAMPs.     

Clusterization-triggered emission: Uncommon luminescence from common materials

π-Conjugated chromophores have been investigated for many years and successful theoretical models have been developed to explain their photophysical properties. However, materials have appeared sporadically that do not fit within these existing models. Some of these materials possess entirely nonconjugated structures based on saturated C–C, C–O or C–N bonds, but their aggregates or solid-state forms show bright visible emission. This phenomenon is termed as clusterization-triggered emission (CTE) and the materials possessing the property are labeled clusteroluminogens. In this review, we provide a brief summary of the recent development of clusteroluminogens. The materials are classified into three categories: polymers (natural and synthetic polymers), small molecules (with and without aromatic rings) and metal clusters. Possible luminescence mechanisms underpinning the different categories of clusteroluminogens are analyzed individually. Finally, we put forward a comprehensive theory of the through-space conjugation (TSC) for these chromophores. Based on the CTE effect and TSC theory, various applications have been envisioned, for example in the areas of process monitoring, structural visualization, sensors, and probes. It is anticipated that this new research direction will bring many breakthroughs, not only in the theoretical areas, but also in these advanced applications of light-emitting materials.     

Molecularly Imprinted Synthetic Antibodies: From Chemical Design to Biomedical Applications

Billions of dollars are invested into the monoclonal antibody market every year to meet the increasing demand in clinical diagnosis and therapy. However, natural antibodies still suffer from poor stability and high cost, as well as ethical issues in animal experiments. Thus, developing antibody substitutes or mimics is a long‐term goal for scientists. The molecular imprinting technique presents one of the most promising strategies for antibody mimicking. The molecularly imprinted polymers (MIPs) are also called “molecularly imprinted synthetic antibodies” (MISAs). The breakthroughs of key technologies and innovations in chemistry and material science in the last decades have led to the rapid development of MISAs, and their molecular affinity has become comparable to that of natural antibodies. Currently, MISAs are undergoing a revolutionary transformation of their applications, from initial adsorption and separation to the rising fields of biomedicine. Herein, the fundamental chemical design of MISAs is examined, and then current progress in biomedical applications is the focus. Meanwhile, the potential of MISAs as qualified substitutes or even to transcend the performance of natural antibodies is discussed from the perspective of frontier needs in biomedicines, to facilitate the rapid development of synthetic artificial antibodies.     

超支化聚合物合成的研究进展

超支化聚合物是一类具有高度支化结构的体型大分子,其独特的结构赋予其具有不同于传统线性聚合物的性能,显示出广阔的应用前景.超支化聚合物的合成是超支化聚合物研究的重要内容,合成方法对超支化聚合物的结构和性能有重要影响.对该领域的最新研究进展进行了归纳介绍,其中主要涉及传统的缩聚聚合、活性聚合、离子聚合、开环聚合以及一些新型的聚合反应,同时论述了各种合成方法的优点和局限性.     

Single Molecule Force Spectroscopy to Compare Natural versus Artificial Antibody–Antigen Interaction

Biorecognition is central to various biological processes and finds numerous applications in virtually all areas of chemistry, biology, and medicine. Artificial antibodies, produced by imprinting synthetic polymers, are designed to mimic the biological recognition capability of natural antibodies, while exhibiting superior thermal, chemical, and environmental stability compared to their natural counterparts. The binding affinity of the artificial antibodies to their antigens characterizes the biorecognition ability of these synthetic nanoconstructs and their ability to replace natural recognition elements. However, a quantitative study of the binding affinity of an artificial antibody to an antigen, especially at the molecular level, is still lacking. In this study, using atomic force microscopy‐based force spectroscopy, the authors show that the binding affinity of an artificial antibody to an antigen (hemoglobin) is weaker than that of natural antibody. The fine difference in the molecular interactions manifests into a significant difference in the bioanalytical parameters of biosensors based on these recognition elements.     

Natural and biomimetic materials for the detection of insulin

Microgravimetric sensors have been developed for detection of insulin by using quartz crystal microbalances as transducers, in combination with sensitive layers. Natural antibodies as coatings were compared with biomimetic materials to fabricate mass-sensitive sensors. For this purpose polyurethane was surface imprinted by insulin, which acts as a synthetic receptor for reversible analyte inclusion. The sensor responses for insulin give a pronounced concentration dependence, with a detection limit down to 1 μg/mL and below. Selectivity studies reveal that these structured polymers lead to differentiation between insulin and glargine. Moreover, antibody replicae were generated by a double imprinting process. Thus, biological recognition capabilities of immunoglobulins are transferred to synthetic polymers. In the first step, natural-immunoglobulin-imprinted nanoparticles were synthesized. Subsequently, these templated particles were utilized for creating positive images of natural antibodies on polymer layers. These synthetic coatings, which are more robust than natural analogues, can be produced in large amount. These biomimetic sensors are useful in the biotechnology of insulin monitoring.     

Bionanocomposites: A New Concept of Ecological,Bioinspired, and Functional Hybrid Materials

Bionanocomposites represent an emerging group of nanostructured hybrid materials. They are formed by the combination of natural polymers and inorganic solids and show at least one dimension on the nanometer scale. Similar to conventional nanocomposites, which involve synthetic polymers, these biohybrid materials also exhibit improved structural and functional properties of great interest for different applications. The properties inherent to the biopolymers, that is, biocompatibility and biodegradability, open new prospects for these hybrid materials with special incidence in regenerative medicine and in environmentally friendly materials (green nanocomposites). Research on bionanocomposites can be regarded as a new interdisciplinary field closely related to significant topics such as biomineralization processes, bioinspired materials, and biomimetic systems. The upcoming development of novel bionanocomposites introducing multifunctionality represents a promising research topic that takes advantage of the synergistic assembling of biopolymers with inorganic nanometer‐sized solids.     

Intermolecular interactions in blends of hyaluronic acid with poly(vinyl alcohol) and ethylene-vinyl alcohol copolymers

Films from blends of hyaluronic acid with poly(vinyl alcohol) and with ethylene-vinyl alcohol copolymers were prepared from solutions in water and dimethylsulfoxide by a casting method. The study of the interactions between the natural and synthetic component has been carried out through thermal and morphological analysis. The results show that the crystallinity of poly(vinyl alcohol) and its copolymers decreases with increasing hyaluronic acid content and these crystallizable polymers exhibit no tendency to crystallize when hyaluronic acid content is more than 80 wt%. The relatively good miscibility in these blends may be due to the capacity of the natural and synthetic component, each with abundant hydroxyl groups, to interact mutually through hydrogen bonding. The presence of such interactions was supported by the observation of the melting point depression of the synthetic component in thermal analysis of the blends. Melting point depression was more accentuated in melt recrystallized blends. These results suggest that the interactions between the two polymers are enhanced if the blends are brought close to the melting point of the synthetic component.     

Composites from Natural Fibers and Soy Oil Resins

The goal of this project is to develop new composites using fibers and resins from renewable resources. The ACRES (Affordable Composites from Renewable Sources) group at the University of Delaware has developed new chemistries to synthesize rigid polymers from plant oils. The resins produced contain at least 50% plant triglycerides and have mechanical properties comparable to commercially available synthetic resins such as vinyl esters, polyesters and epoxies. This project explores the development of all-natural composites by using natural fibers such as hemp and flax as reinforcements in the ACRES resins. Replacing synthetic fibers with natural fibers has both environmental and economic advantages. Unlike carbon and glass fibers, natural fibers are abundantly available from renewable resources. In terms of cost, natural fibers are cheaper than the synthetic alternatives. The natural fibers and plant-based resins have been shown to combine to produce a low cost composite with good mechanical properties. Tensile strength in the 30 MPa range has been obtained for a composite containing about 30 wt% Durafibre Grade 2 flax. The tensile modulus was found to be 4.7 GPa for a 40 wt% flax composite. Similar numbers where obtained for the hemp composites obtained from Hemcore Inc. Composites from renewable resources offer significant potential for new high volume, low cost applications.     

Plasma-modified biomaterials for self-antimicrobial applications

The surface compatibility and antibacterial properties of biomaterials are crucial to tissue engineering and other medical applications, and plasma-assisted technologies have been employed to enhance these characteristics with good success. Herein, we describe and review the recent developments made by our interdisciplinary team on self-antimicrobial biomaterials with emphasis on plasma-based surface modification. Our results indicate that a self-antibacterial surface can be produced on various types of materials including polymers, metals, and ceramics by plasma treatment. Surface characteristics such as roughness, microstructure, chemistry, electronegativity, free energy, hydrophilicity, and interfacial physiochemistry are important factors and can be tailored by using the appropriate plasma-assisted processing parameters. In particular, mechanistic studies reveal that the interfacial physiochemical processes, biocidal agents, and surface free energy are predominantly responsible for the antibacterial effects of plasma-modified biomaterials.     

Bioinspired supramolecular liquid crystals

A brief account on the historical events leading to the discovery of self-assembling dendrons that generate self-organizable supramolecular dendrimers, or supramolecular polymers, and self-organizable dendronized polymers is provided. These building blocks were accessed by an accelerated design strategy that involves structural and retrostructural analysis of periodic and quasi-periodic assemblies. This design strategy mediated the discovery of porous helical supramolecular structures that self-assembled from dendritic dipeptides. Helical porous columns are the closest mimics of biologically related structures, such as tobacco mosaic virus coat, porous transmembrane proteins, porous pathogens and antibiotics. It is expected that this concept will allow one to investigate the structural origin of functions in synthetic supramolecular materials.     

Natural Gums and Modified Natural Gums as Sustained-Release Carriers

Although natural gums and their derivatives are used widely in pharmaceutical dosage forms, their use as biodegradable polymeric materials to deliver bioactive agents has been hampered by the synthetic materials. These natural polysaccharides do hold advantages over the synthetic polymers, generally because they are nontoxic, less expensive, and freely available. Natural gums can also be modified to have tailor-made materials for drug delivery systems and thus can compete with the synthetic biodegradable excipients available in the market. In this review, recent developments in the area of natural gums and their derivatives as carriers in the sustained release of drugs are explored.     

Assessment of Bonelike® graft with a resorbable matrix using an animal model

Synthetic bone grafts have been developed to provide an alternative to autografts and allografts. Bonelike® is a patented synthetic osteoconductive bone graft that mimics the mineral composition of natural bone. In the present preliminary animal studies a user-friendly version of synthetic bone graft Bonelike® have been developed by using a resorbable matrix, Floseal®, as a vehicle and raloxifene hydrochloride as a therapeutic molecule, that is known to decrease osteoclast activity and therefore enhanced bone formation. From histological and scanning electron microscopy evaluations, the use of Bonelike® associated with Floseal® and raloxifene hydrochloride showed that new bone was rapidly apposed on implanted granules and also that the presence of the matrix and therapeutic molecule does not alter the proven highly osteoconductivity properties of Bonelike®. Therefore, this association may be one step-forward for the clinical applications of Bonelike® scaffolds since it is much more easy-to-handle when compared to granular materials.     

Natural gums and modified natural gums as sustained-release carriers

Although natural gums and their derivatives are used widely in pharmaceutical dosage forms, their use as biodegradable polymeric materials to deliver bioactive agents has been hampered by the synthetic materials. These natural polysaccharides do hold advantages over the synthetic polymers, generally because they are nontoxic, less expensive, and freely available. Natural gums can also be modified to have tailor-made materials for drug delivery systems and thus can compete with the synthetic biodegradable excipients available in the market. In this review, recent developments in the area of natural gums and their derivatives as carriers in the sustained release of drugs are explored.     

Light and dark-activated biocidal activity of conjugated polyelectrolytes

This Spotlight on Applications provides an overview of a research program that has focused on the development and mechanistic study of cationic conjugated polyelectrolytes (CPEs) that function as light- and dark-active biocidal agents. Investigation has centered on poly-(phenylene ethynylene) (PPE) type conjugated polymers that are functionalized with cationic quaternary ammonium solubilizing groups. These polymers are found to interact strongly with Gram-positive and Gram-negative bacteria, and upon illumination with near-UV and visible light act to rapidly kill the bacteria. Mechanistic studies suggest that the cationic PPE-type polymers efficiently sensitize singlet oxygen ((1)O(2)), and this cytotoxic agent is responsible for initiating the sequence of events that lead to light-activated bacterial killing. Specific CPEs also exhibit dark-active antimicrobial activity, and this is believed to arise due to interactions between the cationic/lipophilic polymers and the negatively charged outer membrane characteristic of Gram-negative bacteria. Specific results are shown where a cationic CPE with a degree of polymerization of 49 exhibits pronounced light-activated killing of E. coli when present in the cell suspension at a concentration of 1 μg mL(-1).     

Bombyx mori silk fibre and its composite: A review of contemporary developments

Application of natural fibres in composite plastics is gaining popularity in many industries and particularly the automotive industry. Using natural fibres in polymers provides many advantages over other techniques, and the application areas appear limitless. There is currently a shift of paradigm in the automotive industry towards a “green” outlook, due to consumers’ demand for more environmentally friendly vehicles. Natural fibres are biodegradable and are renewable natural source. These two characteristics are most important for disposal of components at end-life. They are recyclable and can be easily converted into thermal energy through combustion, without leaving residue. Among the natural fibres with proven potential application as reinforcement for polymers, Bombyx mori woven silk fibre is one that recently received special attention from researchers. B. mori silk fibre is one of the best fibres discovered in nature, providing high mechanical properties over frequently used natural fibres like sisal, jute, hemp and coir. This review presents a summary of B. mori woven silk fibre and its composite.     

Natural origin biodegradable systems in tissue engineering and regenerative medicine: present status and some moving trends.

The fields of tissue engineering and regenerative medicine aim at promoting the regeneration of tissues or replacing failing or malfunctioning organs, by means of combining a scaffold/support material, adequate cells and bioactive molecules. Different materials have been proposed to be used as both three-dimensional porous scaffolds and hydrogel matrices for distinct tissue engineering strategies. Among them, polymers of natural origin are one of the most attractive options, mainly due to their similarities with the extracellular matrix (ECM), chemical versatility as well as typically good biological performance. In this review, the most studied and promising and recently proposed naturally derived polymers that have been suggested for tissue engineering applications are described. Different classes of such type of polymers and their blends with synthetic polymers are analysed, with special focus on polysaccharides and proteins, the systems that are more inspired by the ECM. The adaptation of conventional methods or non-conventional processing techniques for processing scaffolds from natural origin based polymers is reviewed. The use of particles, membranes and injectable systems from such kind of materials is also overviewed, especially what concerns the present status of the research that should lead towards their final application. Finally, the biological performance of tissue engineering constructs based on natural-based polymers is discussed, using several examples for different clinically relevant applications.     

Past,Present, and Future of Soft-Tissue Prosthetics: Advanced Polymers and Advanced Manufacturing

Millions of people worldwide experience disfigurement due to cancers, congenital defects, or trauma, leading to significant psychological, social, and economic disadvantage. Prosthetics aim to reduce their suffering by restoring aesthetics and function using synthetic materials that mimic the characteristics of native tissue. In the 1900s, natural materials used for thousands of years in prosthetics were replaced by synthetic polymers bringing about significant improvements in fabrication and greater realism and utility. These traditional methods have now been disrupted by the advanced manufacturing revolution, radically changing the materials, methods, and nature of prosthetics. In this report, traditional synthetic polymers and advanced prosthetic materials and manufacturing techniques are discussed, including a focus on prosthetic material degradation. New manufacturing approaches and future technological developments are also discussed in the context of specific tissues requiring aesthetic restoration, such as ear, nose, face, eye, breast, and hand. As advanced manufacturing moves from research into clinical practice, prosthetics can begin new age to significantly improve the quality of life for those suffering tissue loss or disfigurement.