Heavy metals and living systems: An overview

Heavy metals are natural constituents of the earth's crust, but indiscriminate human activities have drastically altered their geochemical cycles and biochemical balance. This results in accumulation of metals in plant parts having secondary metabolites, which is responsible for a particular pharmacological activity. Prolonged exposure to heavy metals such as cadmium, copper, lead, nickel, and zinc can cause deleterious health effects in humans. Molecular understanding of plant metal accumulation has numerous biotechnological implications also, the long term effects of which might not be yet known.     

主动靶向热敏脂质体在肿瘤光热治疗中的应用研究

靶向热敏脂质体是近年来新兴起的一种新型药物载体,其以低毒、靶向、高效等优点受到相关研究者们越来越多的关注。为了进一步提高抗肿瘤药物的靶向性、治疗效果和生物利用度,更多功能更多新靶点的热敏脂质体出现,且在肿瘤的光热治疗中扮演着重要角色。将其与光热治疗相结合,可进一步提高肿瘤的治疗效果。经过查阅和整理近年来国内外相关文献,综述当前主动靶向热敏脂质体的研究现状并展望其在肿瘤光热治疗中的发展前景。     

Synergistic integration of metal nanoclusters and biomolecules as hybrid systems for therapeutic applications

Therapeutic nanoparticles are designed to enhance efficacy, real-time monitoring, targeting accuracy, biocompatibility, biodegradability, safety, and the synergy of diagnosis and treatment of diseases by leveraging the unique physicochemical and biological properties of well-developed bio-nanomaterials. Recently, bio-inspired metal nanoclusters (NCs) consisting of several to roughly dozens of atoms (<2 nm) have attracted increasing research interest, owing to their ultrafine size, tunable fluorescent capability, good biocompatibility, variable metallic composition, and extensive surface bio-functionalization. Hybrid core–shell nanostructures that effectively incorporate unique fluorescent inorganic moieties with various biomolecules, such as proteins (enzymes, antigens, and antibodies), DNA, and specific cells, create fluorescently visualized molecular nanoparticle. The resultant nanoparticles possess combinatorial properties and synergistic efficacy, such as simplicity, active bio-responsiveness, improved applicability, and low cost, for combination therapy, such as accurate targeting, bioimaging, and enhanced therapeutic and biocatalytic effects. In contrast to larger nanoparticles, bio-inspired metal NCs allow rapid renal clearance and better pharmacokinetics in biological systems. Notably, advances in nanoscience, interfacial chemistry, and biotechnologies have further spurred researchers to explore bio-inspired metal NCs for therapeutic purposes. The current review presents a comprehensive and timely overview of various metal NCs for various therapeutic applications, with a special emphasis on the design rationale behind the use of biomolecules/cells as the main scaffolds. In the different hybrid platform, we summarize the current challenges and emerging perspectives, which are expected to offer in-depth insight into the rational design of bio-inspired metal NCs for personalized treatment and clinical translation.Key words: Metal nanoclusters, Biomolecule, Nanoparticles, Hybrid system, Synergistic properties, Fluorescence, Bioprobe, Therapy     

Innovative programs for integrated delivery systems

These programs are most effective under a MCO setting, but will succeed only if there are individuals within the organization to champion these programs. Many pharmacists have taken the lead and are working closely with manufacturers to identify the best use of these programs. These individuals ensure that the programs are implemented and that the appropriate pathways are followed. The pharmacist can assist in identifying those who are not using products appropriately. Using the manufacturer's resources (sales force) to supply the provider with educational material can help the provider follow the pathways and focus on appropriate use. The pharmacist can monitor the data and offer suggestions on program modifications. Therefore, the pharmacist plays a key role in meeting the challenges presented by outcomes performance programs and in creating an opportunity for the patient care organization to achieve its financial goals. With the MCO and manufacturer as partners, these programs will be successful and can increase the quality of care to MCO members who receive care in an institutional or community managed care setting.     

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.     

Self-assembling peptides: potential role in tumor targeting

This review focuses on the application of two classes of peptides, i.e., self-assembling peptides (SAPs) and cell-targeting peptides (CTPs), in the development of nanocarrier delivery systems. Self-assembling peptides are emerging in a wide range of biomedical and bioengineering applications and fall into several classes, including peptide amphiphilies, bolaamphiphile peptides, cyclic peptides, and ionic complementary peptides, which can be found naturally or synthesized. The advantage of synthesizing peptides is that their self-assembling properties can be exploited to form desirable structures for various applications. Another, unique property of self-assembling peptides, is stimuli-responsibility in different environments including various pHs, temperatures, ionic strengths, etc. These characteristics make peptides applicable in a wide range of biomaterials in drug discovery. This study reviews the design principles of well-known self-assembling peptides, as well as their physical/chemical properties. In addition, it discusses the therapeutic cancer-targeting peptides and current combinatorial peptide library methods used to identify targeting peptides. Cancer-targeting peptides can target either tumor cell surfaces or tumor vasculature. The RGD peptide is one of the first tumor-targeting peptides that can bind to self-assembling peptides or any other nanocarrier to improve the therapeutic efficiency of targeting drug delivery systems.     

Fluorescent imaging in living systems.

The use of fluorescent imaging techniques in the study of living biological systems has become an important experimental tool in modern biology. Over recent years novel imaging technologies have been developed and older techniques refined. New fluorescent probes continue to become available and the ways in which they are used is increasingly creative. Commonly used imaging methods such as confocal and multiphoton microscopy, when combined with techniques such as fluorescence resonance energy transfer (FRET) and fluorescence lifetime imaging (FLIM), can provide powerful strategies with which to study molecular events in intact cells.     

New approaches in drug delivery systems: application for diabetes treatment

Advanced drug delivery systems present indubitable advantages for drug administration. During the past three decades, new approaches for the development of new carriers for this topic have been suggested. This led to explosion of publication activity in the area. This article reviews briefly the history of the topic and focuses on general concepts in the issue. One of the most crucial properties of advanced delivery systems is their ability to be well controlled in terms of a carrier structure which is responsible for an optimal drug release. Here we describe new polymerization technologies which consider this particular aspect. A special attention is paid to the preparation of materials by LRP (Living Radical Polymerization) and perspectives of its practical application to the treatment of single diseases. Due to the epidemic scale of Diabetes mellitus, novel drug delivery systems play an important role in and are highly relevant for improved treatment of worldwide permanently growing sub-population of diabetic patients. Type 1 is the insulin-dependent diabetes which accounts for 5 till 10 percent of the whole pool of diabetic cases and currently attracts main attention in research activity devoted to the development of advanced drug delivery systems. Minimal invasive insulin administration approaches and/or improvement of pancreatic activity in own insulin production is the main goal of novel drug delivery systems highly desirable for advanced treatment of diabetic patients with both type 1 and type 2 of the disease.     

Self-assembling peptides and their potential applications in biomedicine

For many years, peptides have been known to self-assemble to form nano- and micro-scale structures. Their nature of assembly and assembled morphology has since been investigated as this area of research has important implications for the development of both drug delivery and tissue regeneration. In this article, we explore the process of peptide self-assembly in vivo, and experiments that exploit the structures formed. Particular focus is directed towards diphenylalanine, the simplest self-assembling peptide, which generally forms tube-like structures on assembly. In addition, different peptides that may assemble into a range of other morphologies are highlighted and potential applications in regenerative medicine and drug delivery discussed.     

乌贼墨纳米颗粒制备工艺优化及肿瘤光热治疗应用研究

目的 分离纯化乌贼墨纳米颗粒(squid ink nanoparticles,SINPs),开展材料学表征,考察其肿瘤光热治疗(photothermal therapy,PTT)作用。方法 通过搅拌、超声和离心纯化出SINPs,在近红外激光(Near Infra-Red,NIR)照射下考察其体外光热转化效果,采用CCK-8法测定细胞存活率,通过对小鼠瘤内注射给药的同时给予激光照射研究其体内抑瘤效果。结果 制备的SINPs粒径为(212 ± 1.4) nm,Zeta电位为(-14.5 ± 0.7) mV。测定其光热转化效率为35.5%,说明其可作为一种光热转化剂。800 μg/mL的SINPs在808 nm激光照射下小鼠乳腺癌细胞(4T1)的存活率为67.3%,表明SINPs联合PTT对4T1细胞有一定的细胞毒性,此外,在荷瘤小鼠体内,空白组瘤重为SINPs高+laser组瘤重的2.3倍,说明SINPs联合PTT有一定的抗瘤作用。结论 SINPs联合PTT能显著抑制荷瘤小鼠体内肿瘤组织的生长。作为一种天然纳米材料,SINPs具有良好的肿瘤PTT作用,提示其除传统药理作用外,作为天然、安全的纳米材料或载体,在肿瘤光学治疗领域具有一定应用前景。     

Lipid-based supramolecular systems for topical application: A preformulatory study

This article describes the production and characterization of monoglyceride-based supramolecular systems by a simple processing technique, avoiding time-consuming procedures, high energy input, and the use of organic solvents. A preformulatory study was performed to study the influence of the experimental parameters on the production of monoglyceride-based disperse systems. In particular the effects of (1) stirring speed, (2) type and concentration of monoglyceride mixture, and (3) type and concentration of surfactant were investigated on the recovery, fraction of larger particles, mean diameter, and shape of smaller particles (so called nanosomes). Dispersions were first characterized by optical microscopy and freeze-fracture electron microscopy. The mean diameter of standard nanosomes, analyzed by photon correlation spectroscopy (PCS) after elimination of larger particles by filtration, was 193.5 nm. Cryotransmission electron microscopy studies, conducted in order to investigate the structure of dispersions, showed the coexistence of vesicles and particles characterized by a cubic organization. X-ray diffraction data revealed the coexistence of 2 different cubic phases, the first being a bicontinuous cubic phase of spatial symmetry Im3m (Q²²⁹) and the second belonging to the Pn3m spatial symmetry. A study on the stability of monoglyceride-based dispersions based on macroscopical analysis of organoleptic properties and dimensional analysis by time was performed after elimination of larger particles by filtration. Organoleptic and morphological features do not change by time, appearing free from phase-separation phenomena for almost 1 year from production. PCS studies showed that nanosomes undergo an initial increase in mean diameter within the first month following production; afterwards they generally maintain their dimensions for the next 4 months.     

Ligand-binding proteins: their potential for application in systems for controlled delivery and uptake of ligands

Unstable or harmful agents, such as drugs, vitamins, flavors, pheromones, and catalysts, for use in pharmaceutics, personal care, functional foods, crop protection, laboratories, offices, and industrial processes, require stabilization against oxidation and degradation or shielding from sensitive environments. Therefore, binding them to carriers with high affinity and selectivity for targeting to the right environment and subsequent controlled release is beneficial, especially if this allows improved control of (stimulus-induced) release. Proteins often possess one or more of these properties, whereas modern biotechnology and bioinformatics provide an increasing number of tools to engineer and adapt these properties. Carrier systems are now developed that incorporate proteins as the central ligand-binding component, e.g., lectins for glucose-triggered release of glycosylated insulin and bispecific antibodies for brain targeting of drugs, but ligand-binding proteins can potentially be used in many other applications. Collectively, the proteins available in nature bind an impressive variety of ligands and non-natural analogs. In this light, various ligand-binding protein classes are surveyed, including biotin-, lipid-, immunosuppressant-, insect pheromone-, phosphate-, and sulfate-binding proteins, as well as bacterial periplasmic proteins, lectins, serum albumins, immunoglobulins, and inactivated enzymes. Disadvantages, such as enzymatic degradation or immunogenicity, associated with the pharmaceutical use of certain proteins can be avoided by incorporating these proteins in more complex carrier and targeting systems. In other applications, this may not be necessary. The enclosure of high-affinity (potentially stimulus-sensitive) binding proteins within an envelope that acts as a diffusion barrier for the ligand may provide excellent slow release. Many possibilities seem to be as yet unexplored.     

微生态活菌制剂在儿科的临床应用

自 192 8年ＡｌｅｘａｎｄｅｒＦｌｅｍｉｎｇ发现青霉素以来 ,抗生素已广泛应用于临床 ,人们认识到了其对恢复健康的重要价值 ,同时也逐渐认识到了滥用抗生素或治疗措施不当 ,可导致菌群失调和耐药菌株产生 ,造成或加重微生态失衡 ,使得人们越来越重视研究用于调节微生态失衡的微生态疗法。微生态活菌制剂在儿科的临床研究及应用就是其中一个重要方面。1　微生态活菌制剂1 1　概念　微生态活菌制剂指用人或动物正常优势细菌群制成的生物制剂。临床上通过使用这些对人体有益的活菌 ,抑制过度繁殖并引起疾病的有害细菌种群 ,同时促进正常优势…     

Nano in nano: Biosynthesized gold and iron nanoclusters cargo neoplastic exosomes for cancer status biomarking

Timely detection is crucial for successful treatment of cancer. The current study describes a new approach that involves utilization of the tumor cell environment for bioimaging with in-situ biosynthesized nanoscale gold and iron probes and subsequent dissemination of Au-Fe nanoclusters from cargo exosomes within the circulatory system. We have isolated the Au-Fe cargo exosomes from the blood of the treated murine models after in situ biosyntheses from their respective pre-ionic solutions (HAuCl₄, FeCl₂), whereas Na₂SeO₃ supplementation added into Au lethal effect. The microarray data of various differentially expressed genes revealed the up-regulated tumor ablation and metal binding genes in SGC-7901 cell lines after treatment with Au-Fe-Se triplet ionic solution. The isolation of Au-Fe nanoclusters cargo exosomes (nano in nano) after secretion from deeply seated tumors may help in early diagnosis and reveal the tumor ablation status during and after the relevant treatment like radio-chemo therapies et al.     

The cellular immunotherapy of integrated photothermal anti-oxidation Pd–Se nanoparticles in inhibition of the macrophage inflammatory response in rheumatoid arthritis

Reducing the inflammatory response is a major goal in the therapy of rheumatoid arthritis (RA). Herein, we integrated palladium nanoparticles (Pd NPs) with selenium nanoparticles (Se NPs) and obtained a multiple nanosystem (Pd@Se-HA NPs) that could simultaneously scavenge hydroxyl radicals (⋅OH) and provide a photothermal effect. The Pd@Se-HA NPs were constructed by a simple self-assembly method in which Se NPs were electrostatically bonded to Pd NPs; hyaluronic acid (HA) was linked to the NPs by ester bonding to provide macrophage targeting ability. The experiments show that the combined therapy of eliminating ⋅OH with Se NPs and utilizing PTT with Pd NPs could effectively reduce the inflammatory response in macrophages more effectively than either individual NP treatment. In addition, the outer layer of HA could specifically target the CD44 receptor to enhance the accumulation of Pd@Se NPs at the lesion, further enhancing the therapeutic effect. After treatment for 15 days, the Pd@Se-HA NPs nearly eliminated the inflammatory response in the joints of mice in an induced RA model, and prevented joint damage and degradation.KEY WORDS: Rheumatoid arthritis, Inflammatory response, Photothermal therapy, Anti-oxidation therapy, Core‒shell structure     

Transgenic fish systems and their application in ecotoxicology

Abstract

The use of transgenics in fish is a relatively recent development for advancing understanding of genetic mechanisms and developmental processes, improving aquaculture, and for pharmaceutical discovery. Transgenic fish have also been applied in ecotoxicology where they have the potential to provide more advanced and integrated systems for assessing health impacts of chemicals. The zebrafish (Daniorerio) is the most popular fish for transgenic models, for reasons including their high fecundity, transparency of their embryos, rapid organogenesis and availability of extensive genetic resources. The most commonly used technique for producing transgenic zebrafish is via microinjection of transgenes into fertilized eggs. Transposon and meganuclease have become the most reliable methods for insertion of the genetic construct in the production of stable transgenic fish lines. The GAL4–UAS system, where GAL4 is placed under the control of a desired promoter and UAS is fused with a fluorescent marker, has greatly enhanced model development for studies in ecotoxicology. Transgenic fish have been developed to study for the effects of heavy metal toxicity (via heat-shock protein genes), oxidative stress (via an electrophile-responsive element), for various organic chemicals acting through the aryl hydrocarbon receptor, thyroid and glucocorticoid response pathways, and estrogenicity. These models vary in their sensitivity with only very few able to detect responses for environmentally relevant exposures. Nevertheless, the potential of these systems for analyses of chemical effects in real time and across multiple targets in intact organisms is considerable. Here we illustrate the techniques used for generating transgenic zebrafish and assess progress in the development and application of transgenic fish (principally zebrafish) for studies in environmental toxicology. We further provide a viewpoint on future development opportunities.     

纳米分散系的制备与应用*

作为一种新型给药系统，纳米分散系可提高药物在靶部位的浓度，改变其体内分布和药动学过程，达到提高疗效和降低毒性的作用。现综述了纳米分散系的主要类型、制备方法以及在药学领域中的应用进展。作为一种新型给药系统，纳米分散系具有广阔的开发与应用前景。     

Self-assembling peptides-based nano-cargos for targeted chemotherapy and immunotherapy of tumors: recent developments,challenges, and future perspectives

Self-assembling peptides (SAPs) have enormous potential in medical and biological applications, particularly noninvasive tumor therapy. SAPs self-assembly is governed by multiple non-covalent interactions and results in the formation of a variety of morphological features. SAPs can be assembled in a variety of ways, including chemical conjugation and physical encapsulation, to incorporate multiple bioactive motifs. Peptide-based nanomaterials are used for chemotherapy, delivery vehicles, immunotherapy, and noninvasive tumor therapies (e.g. photodynamic therapy) by employing the self-assembling properties of peptides. The recent increase of SAPs is almost entirely due to their excellent biocompatibility, responsiveness toward tumor microenvironment, multivalency, and structural versatility. Synergistic therapy is a more effective and powerful approach to treat the tumor. Notably, SAPs can be used to subtly combine various treatments. Importantly, SAPs are capable of subtly making the combination of various treatments. This review describes mechanisms of peptides self-assemble into various structures and their biomedical applications with a focus on possible treatments.