Single-walled carbon nanotubes mediated targeted tamoxifen delivery system using aspargine-glycine-arginine peptide

Abstract

An aspargine-glycine-arginine (NGR) peptide modified single-walled carbon nanotubes (SWCNTs) system, developed by a simple non-covalent approach, could be loaded with the anticancer drug tamoxifen (TAM). This TAM-loaded NGR modified SWCNTs (TAM/NGR-SWCNTs) not only retained both optical properties of SWCNTs and cytotoxicity of TAM, but also could accumulate in tumors and enter into 4T1 cells, which facilitated combination chemotherapy with photothermal therapy in one targeting system. Enhanced cellular uptake, antitumor effect and cell apoptosis of TAM/NGR-SWCNTs on 4T1 cells were observed in vitro, compared with the TAM solution, TAM/SWCNTs and photothermal therapy alone. In vivo investigation of TAM/NGR-SWCNTs in tumor-bearing mice further confirmed that this system possessed much higher tumor targeting capacity and antitumor efficacy than the control, especially with the near-infrared-laser irradiation treatment. Moreover, it demonstrated negligible systematic toxicity through the histopathological analysis. All these results suggest TAM/NGR-SWCNTs are promising for high targeted efficiency and treatment efficacy and low side effects of future cancer therapy by synergistic effect of chemo-photothermal combination.     

Native albumin for targeted drug delivery

Importance in the field: Activated cells metabolize albumin to cover their increased need for amino acids and energy. In inflamed, diseased and malignant tissue, extravasation of macromolecules into the tissue is upregulated. Drug carriers such as albumin have been used to target specifically diseased and malignant cells, resulting in higher efficacy of treatment and reduced side effects.

Areas covered in this review: Owing to its advantageous biochemical and pharmacological properties, albumin has been regarded as an interesting candidate as a drug carrier. Covalent coupling to albumin carries drugs specifically to tumors and sites of inflammation, leading to reduced side effects as long as the native structure of albumin is unchanged. In this review, the means of coupling drugs to native albumin as well as exemplary studies for the use of albumin as drug carrier are summarized and discussed.

What the reader will gain: An overview of the state-of-the-art using albumin as drug carrier for specific accumulation in tumors and inflammatory cells using the advantageous properties of native albumin is given in this review.

Take home message: Native albumin is an effective drug carrier to sites of inflammation or malignancy.     

Filled carbon nanotubes in biomedical imaging and drug delivery

Introduction: Carbon nanotubes have been advocated as promising candidates in the biomedical field in the areas of diagnosis and therapy. In terms of drug delivery, the use of carbon nanotubes can overcome some limitations of ‘free’ drugs by improving the formulation of poorly water-soluble drugs, allowing targeted delivery and even enabling the co-delivery of two or more drugs for combination therapy. Two different approaches are currently being explored for the delivery of diagnostic and therapeutic agents by carbon nanotubes, namely attachment of the payload to the external sidewalls or encapsulation into the inner cavities. Although less explored, the latter confers additional stability to the chosen diagnostic or therapeutic agents, and leaves the backbone structure of the nanotubes available for its functionalization with dispersing and targeting moieties. Several drug delivery systems and diagnostic agents have been developed in the last years employing the inner tubular cavities of carbon nanotubes.

Areas covered: The research discussed in this review focuses on the use of carbon nanotubes that contain in their interior drug molecules and diagnosis-related compounds. The approaches employed for the development of such nanoscale vehicles along with targeting and releasing strategies are discussed.

Expert opinion: The encapsulation of both biomedical contrast agents and drugs inside carbon nanotubes is further expanding the possibilities to allow an early diagnosis and treatment of diseases.     

Pharmacological and functional magnetic resonance imaging techniques in CNS drug discovery

Functional magnetic resonance imaging (fMRI) has transformed cognitive neuroscience over the past 10 – 15 years, allowing clinical researchers unprecedented access to the functioning of the human brain under many different conditions including motor, sensory and cognitive stimulation. During the past 5 years, increasing interest has also focused on mapping pharmacologically induced changes in human brain activity produced following exposure to psychoactive agents such as amphetamine and cocaine, and is now frequently termed pharmacological MRI (phMRI). Unfortunately, preclinical fMRI and phMRI studies have not kept pace with human research, largely due to numerous technical hurdles inherent in small laboratory animal imaging, as well as the high cost of necessary equipment. However, this is now set to change with significant investment being made across academic and industry laboratories, as researchers attempt to tap into the huge potential of this noninvasive and powerful translational tool. This review introduces the principles and fundamental assumptions behind the technologies, details some important applications of fMRI and phMRI within a CNS research environment, and examines the potential future impact of the technology.     

Radionuclide imaging of drug delivery for patient selection in targeted therapy

Introduction: During the last decade, numerous antibodies and tyrosine kinase inhibitors have been developed for cancer treatment. However, only a limited number of these agents have been shown to significantly improve survival of patients. Therefore, it is of crucial importance to identify the subset of patients who benefit from targeted therapy. Biomarkers can play an important role in selecting the right drug for the right patient.

Areas covered: In this review, the potential role of molecular imaging of drug delivery for patient selection in targeted therapy will be discussed. The advantages and limitations of molecular imaging will be compared to those of conventional biomarkers. Moreover, we will address the factors that affect imaging of drug delivery, such as target expression, type of drug, in vivo accessibility of the receptor (e.g., vascular density, vascular permeability, interstitial pressure), enhanced permeability and retention (EPR) effect, receptor internalization, tracer protein dose and timing of imaging.

Expert opinion: Molecular imaging of drug delivery clearly has potential for patient selection for targeted therapy. The main advantage of this technique is that not only can antigen expression be measured noninvasively but also target accessibility is taken into account. However, up to now, most of these studies have been performed in preclinical models. Therefore, future research should focus on bringing promising tracers to the clinic, preferable in an early stage of drug development in order to test their potential role as a biomarker.     

Thermo-responsive magnetic liposomes for hyperthermia-triggered local drug delivery

We prepared and characterised thermo-responsive magnetic liposomes, which were designed to combine features of magnetic targeting and thermo-responsive control release for hyperthermia-triggered local drug delivery. The particle size and zeta-potential of the thermo-responsive magnetic ammonium bicarbonate (MagABC) liposomes were about 210?nm and ?14?mV, respectively. The MagABC liposomes showed encapsulation efficiencies of about 15% and 82% for magnetic nanoparticles (mean crystallite size 12?nm) and doxorubicin (DOX), respectively. The morphology of the MagABC liposomes was visualised using transmission electron microscope (TEM). The MagABC liposomes showed desired thermo-responsive release. The MagABC liposomes, when physically targeted to tumour cells in culture by a permanent magnetic field yielded a substantial increase in intracellular accumulation of DOX as compared to non-magnetic ammonium bicarbonate (ABC) liposomes. This resulted in a parallel increase in cytotoxicity for DOX loaded MagABC liposomes over DOX loaded ABC liposomes in tumour cells.     

Model-based optimized steering and focusing of local magnetic particle concentrations for targeted drug delivery

Magnetic drug targeting (MDT) is an application in the field of targeted drug delivery in which magnetic (nano)particles act as drug carriers. The particles can be steered toward specific regions in the human body by adapting the currents of external (electro)magnets. Accurate models of particle movement and control algorithms for the electromagnet currents are two of the many requirements to ensure effective drug targeting. In this work, a control approach for the currents is presented, based on an underlying physical model that describes the dynamics of particles in a liquid in terms of their concentration in each point in space. Using this model, the control algorithm determines the currents generating the magnetic fields that maximize the particle concentration in spots of interest over a period of time. Such an approach is computationally only feasible thanks to our innovative combination of model order reduction with the method of direct multiple shooting. Simulation results of an in-vitro targeting setup demonstrated that a particle collection can be successfully guided toward the targeted spot with limited dispersion through a surrounding liquid. As now present and future particle behavior can be taken into account, and non-stationary surrounding liquids can be dealt with, a more precise and flexible targeting is achieved compared to existing MDT methods. This proves that the presented methodology can bring MDT closer to its clinical application. Moreover, the developed model is compatible with state-of-the-art imaging methods, paving the way for theranostic platforms that combine both therapy as well as diagnostics.     

A33 antibody-functionalized exosomes for targeted delivery of doxorubicin against colorectal cancer

Exosomes have emerged as a promising drug carrier with low immunogenicity, high biocompatibility and delivery efficiency. Here in, we isolated exosomes from A33-positive LIM1215 cells (A33-Exo) and loaded them with doxorubicin (Dox). Furthermore, we coated surface-carboxyl superparamagnetic iron oxide nanoparticles (US) with A33 antibodies (A33Ab-US), expecting that these A33 antibodies on the surface of the nanoparticles could bind to A33-positive exosomes and form a complex (A33Ab-US-Exo/Dox) to target A33-positive colon cancer cells. The results showed that A33Ab-US-Exo/Dox had good binding affinity and antiproliferative effect in LIM1215 cells, as shown by increased uptake of the complex. In vivo study showed that A33Ab-US-Exo/Dox had an excellent tumor targeting ability, and was able to inhibit tumor growth and prolong the survival of the mice with reduced cardiotoxicity. In summary, exosomes functionalized by targeting ligands through coating with high-density antibodies may prove to be a novel delivery system for targeted drugs against human cancers.     

Nanosystems for simultaneous imaging and drug delivery to T cells

The T-cell response defines the pathogenesis of many common chronic disease states, including diabetes, rheumatoid arthritis, and transplant rejection. Therefore, a diagnostic strategy that visualizes this response can potentially lead to early therapeutic intervention, avoiding catastrophic organ failure or prolonged sickness. In addition, the means to deliver a drug dose to those cells in situ with the same specificity used to image those cells would provide for a powerful therapeutic alternative for many disease states involving T cells. In this report, we review emerging nanosystems that can be used for simultaneous tracking and drug delivery to those cells. Because of their versatility, these systems--which combine specific receptor targeting with an imaging agent and drug delivery--are suited to both basic science and applications, from developing therapeutic strategies for autoimmune and alloimmune diseases, to noninvasive tracking of pathogenic T-cell migration.     

Stimuli-sensitive drug delivery systems for site-specific antibiotic release

Site-specific delivery of antibiotics has always been a high-priority area in pharmaceutical research. Conventionally used antibiotics suffer several limitations, such as low accumulation and penetration in diseased cells/tissues, limited bioavailability of drugs, drug resistance, and off-target toxicity. To overcome these limitations, several strategies have been exploited for delivering antibiotics to the site of infection, such as the use of stimuli-responsive antibiotic delivery systems, which can release antibiotics in a controlled and timely fashion. These stimuli can either be exogenous (light, magnetism, ultrasound, and electrical) or endogenous (pH, redox reactions, and enzymatic). In this review, we present a summary of recent developments in the field of stimuli-based targeted drug delivery systems for the site-specific release of antibiotics.     

前列腺癌的磁共振成像临床研究进展

前列腺癌是老年男性常见肿瘤,早期发现及干预治疗特别重要.磁共振成像被公认为是前列腺癌早期诊断及评价分期最好的影像学方法之一.随着磁共振新技术的发展和临床应用,前列腺癌的磁共振影像学诊断已从形态学发展到分子水平.该文就前列腺癌的 MRI临床研究进展进行综述.     

Layer-by-layer capsules for magnetic resonance imaging and drug delivery

Layer-by-layer (LbL) self-assembled polyelectrolyte capsules have demonstrated their unique advantages and capability in drug delivery applications. These ordered micro/nano-structures are also promising candidates as imaging contrast agents for diagnostic and theranostic applications. Magnetic resonance imaging (MRI), one of the most powerful clinical imaging modalities, is moving forward to the molecular imaging field and requires the availability of advanced imaging probes. In this review, we are focusing on the design of MRI visible LbL capsules, which incorporate either paramagnetic metal-ligand complexes or superparamagnetic iron oxide (SPIO) nanoparticles. The design criteria cover the topics of probe sensitivity, biosafety, long-circulation property, targeting ligand decoration, and drug loading strategies. Examples of MRI visible LbL capsules with paramagnetic or superparamagnetic moieties were given and discussed. This carrier platform can also be chosen for other imaging modalities.     

Protease-triggered bioresponsive drug delivery for the targeted theranostics of malignancy

Proteases have a fundamental role in maintaining physiological homeostasis, but their dysregulation results in severe activity imbalance and pathological conditions, including cancer onset, progression, invasion, and metastasis. This striking importance plus superior biological recognition and catalytic performance of proteases, combining with the excellent physicochemical characteristics of nanomaterials, results in enzyme-activated nano-drug delivery systems (nanoDDS) that perform theranostic functions in highly specific response to the tumor phenotype stimulus. In the tutorial review, the key advances of protease-responsive nanoDDS in the specific diagnosis and targeted treatment for malignancies are emphatically classified according to the effector biomolecule types, on the premise of summarizing the structure and function of each protease. Subsequently, the incomplete matching and recognition between enzyme and substrate, structural design complexity, volume production, and toxicological issues related to the nanocomposites are highlighted to clarify the direction of efforts in nanotheranostics. This will facilitate the promotion of nanotechnology in the management of malignant tumors.     

Nanotech approaches to drug delivery and imaging

Nanotechnology, a multidisciplinary scientific undertaking, involves creation and utilization of materials, devices or systems on the nanometer scale. The field of nanotechnology is currently undergoing explosive development on many fronts. The technology is expected to create innovations and play a critical role in various biomedical applications, not only in drug delivery, but also in molecular imaging, biomarkers and biosensors. Target-specific drug therapy and methods for early diagnosis of pathologies are the priority research areas where nanotechnology would play a vital role. This review considers different nanotechnology-based drug delivery and imaging approaches, and their economic impact on pharmaceutical and biomedical industries.     

Drug delivery targets and systems for targeted treatment of rheumatoid arthritis

Rheumatoid arthritis (RA) is an immune-mediated inflammatory disease that selectively attacks human joints. The common non-targeted treatment approaches lead to obvious side effect and systemtic complication for RA patients. Therefore, targeted drug delivery for treatment of RA has gained much attetntion in the past few years. In this paper, we reviewed the potential targets (folate receptor, angiogenesis, matrix metalloproteases, selectins, vasoactive intestinal peptide receptor andFc-γ receptor) that could be utilised to facilitate the specific delivery of drugs to the inflammed synovium and also presented different drug delivery systems for targeting RA, including the liposomes, various types of nanoparticles, polymeric micelles and the macromolecular prodrugs. The strategies combining nanotechnologies and ligand mediated active targeting for RA would be emphatically illustrated, which was expected to be helpful for identifying technologies and drug delivery methods for targeted treatment of RA.     

The role of macromolecular architecture in passively targeted polymeric carriers for drug and gene delivery

The use of polymeric carriers for drug delivery has become increasingly popular because of the ability to easily tune the physical and biological properties of macromolecules. With the growing commercial accessibility of branched and dendritic polymers, their incorporation into polymeric carriers is being explored with increased frequency. However, while a handful of systematic studies have explored the use of branched macromolecules for drug delivery, the role of polymer architecture in optimizing the polymeric carriers is not yet fully understood. Herein, the authors summarize the effect that architecture has on the basic physical properties of polymers, and review our preliminary understanding of the architectural effects on polymer-assisted drug delivery.     

Polymeric nanofibers: targeted gastro-retentive drug delivery systems

Background: Conventional oral dosage forms exhibit poor/low bioavailability due to incomplete release of drug and short residence time at the absorption site. Gastro-retentive drug delivery system (GRDDS) is particularly used to improve bioavailability of the drugs, which have narrow absorption window down in the levels of gastrointestinal tract and also to treat local disorders.

Purpose: The purpose of this review is to describe the utility of the nanofibers as gastro-retentive dosage form. From last few decades, formulation scientists have put extensive efforts to develop suitable gastro-retentive drug delivery system, which is appropriate for commercialization. Current approaches used for preparation of gastro-retentive drug delivery system offers limited functional features to control the floating behavior. Recently, an extensive research has been developed to improve the gastric residence time by using nanofibers, which ultimately leads to the increased bioavailability of the drug. Multiple functional features and unique properties of nanofibers improve its gastro retention.

Conclusion: Nanofiber system provides stomach-specific drug release for longer duration; moreover, increased local action of the drug due to prolonged contact time with the gastric mucosa. Thus, the nanofiber system promises to be the potential approach for gastric retention drug delivery system.     

核磁共振成像与阿尔采末病早期诊断

随着核磁共振成像技术的不断发展,它在诊断和早期诊断阿尔采末病的过程中的作用越来越突出。本文对近年来的核磁共振成像三维测量、功能性核磁共振成像、核磁共振波谱成像和核磁共振弥散张量成像4种技术对阿尔采末病的研究结果进行了综述,并阐述了以上4种核磁共振成像技术之于诊断和早期诊断阿尔采末病的研究前景。     

磁共振扩散加权成像对乳腺癌的诊断价值

目的 探讨磁共振扩散加权成像(DWI)的表观扩散系数(ADC)值对乳腺肿块鉴别诊断价值,提高乳腺癌的诊断特异性.方法 对93例105个乳腺肿块患者行常规MR平扫DWI成像,测量ADC值.结果 37例43个良性病灶的平均ADC值:(1.37±0.36)×10-3 mm2/s,最大、最小ADC差值(0.63±0.19)×10-3mm2/s;58例62个恶性病灶的平均ADC值:(0.90±0.53)×10-3mm2/s,最大、最小ADC差值(0.91±0.27)×10-3 mm2/s;两者平均ADC值,最大、最小ADC差值的差异均有统计学意义(均P＜0.01).绘制诊断良、恶性病变ADC值ROC曲线,以1.1×10-3mm2/s作为临界值作为判断良、恶性的标准,敏感性为67％,特异性为72％;以1.0×10-3mm2/s为临界值,特异性可提高到84％.而敏感度降为60％.以最大、最小ADC差值0.75×10-3mm2/s为临界值,敏感性为67％,特异性为68％,如以0.80×10-3mm2/s为临界值,敏感性为53％,特异性为82％.结论 DWI的ADC值对乳腺良恶性病变的鉴别诊断具有一定的意义.     

HSA nanocapsules functionalized with monoclonal antibodies for targeted drug delivery

The chronic autoimmune disorder rheumatoid arthritis (RA) affects millions of adults and children every year. Chronically activated macrophages secreting enzymes and inflammatory cytokines play a key role in RA. Distinctive marker molecules on the macrophage surface could be used to design a targeted drug delivery device for the treatment of RA without affecting healthy cells and tissues. Here, different methods for covalent attachment of antibodies (mAb) recognizing MHC class II molecules found on macrophages onto human serum albumin (HSA) nanocapsules were compared. HSA nanocapsules were prepared with a hydrodynamic diameter of 500.7 ± 9.4 nm and a narrow size distribution as indicated by a polydispersity index (PDI) of 0.255 ± 0.024. This was achieved by using a sonochemical process avoiding toxic cross linking agents and emulsifiers. Covalent binding of mAb on the surface of HSA nanocapsules was realized using polyethyleneglycol (PEG)₃₀₀₀ as spacer molecule. The presence of mAb was confirmed by confocal laser scanning microscopy (CLSM) and enzyme-linked immunosorbent assay (ELISA). Specific binding of mAb-HSA nanocapsules to MHC class II molecules on antigen-presenting cells was demonstrated by flow cytometry analysis.