Transferrin-mediated fullerenes nanoparticles as Fe2+-dependent drug vehicles for synergistic anti-tumor efficacy

Artesunate (AS) is an iron-dependent drug, which has been used extensively as anti-malarial drugs worldwide with no obvious side effects. Recently, studies have shown that AS also possess profound cytotoxicity against tumor cells. However, simultaneous delivery of hydrophobic AS and Fe²⁺ into tumor cells remains a major challenge. Herein, we report a new kind of active-targeting preparations which could not only specially target to tumor cells but also synchronously transfer AS and irons into tumor tissue. In this study, hyaluronic acid (HA) was grafted onto fullerene to get a water-soluble biomaterial (HA-C60) with excellent biocompatibility, and then combined with transferrin (Tf) to obtain a multi-functional drug delivery system (HA-C60-Tf) with significant tumor-targeting efficacy and powerful photodynamic therapy capacity. Finally, AS was adsorbed on HA-C60-Tf with a high loading efficacy of 162.4% (weight ratio of AS: HA-C60-Tf). Compared with free AS, remarkably enhanced antitumor efficacy of AS-loaded HA-C60-Tf nanoparticles was realized both in a cultured MCF-7 cells in vitro and in a tumor-bearing murine model in vivo, due to increased intracellular accumulation of AS in tumor and activated mechanism by co-delivery of Tf and AS analogs. Furthermore, with laser irradiation in vivo, the relative tumor volume (V/V₀) of HA-C60-Tf/AS declined by half, from 1.72 ± 0.12 to 0.84 ± 0.07, suggesting a new way with multi-mechanism for tumor treatment was developed.     

Pioneering Remotely Piloted Aerial Systems (Drone) Delivery of a Remotely Telementored Ultrasound Capability for Self Diagnosis and Assessment of Vulnerable Populations—the Sky Is the Limit

Journal of Digital Imaging - Remotely Piloted Aerial Systems (RPAS) are poised to revolutionize healthcare in out-of-hospital settings, either from necessity or practicality, especially for remote...     

道路交通伤机动车碰撞类型比较研究

目的：研究道路交通伤的临床流行病学特点与机动车碰撞类型的关系。方法；将14779例由机动车碰撞所致的道路交通伤患者按其碰撞类型分组，对致伤方式、受伤部位、创伤严重程度、生理改变以及预测预后等方面进行比较和统计学分析。结果：机动车与行人和机动车碰撞为道路交通伤机动车主要碰撞类型，机动车与行人和摩托车碰撞致伤者损伤严重程度评分（ISS）分值较高，生存概率（Ps )预测值较低，且死亡所占比例较大（51．98％，92／177）；2个部位损伤为各种碰撞类型的主要受伤形式，其中头部及四肢骨骼伤较为常见，胸及腹部简明损伤定级（AIS）高会值伤较多；车外人员伤后生理紊乱较车内人员更为显著（P＜0．0）。结论：机动车所致的道路交通临床特点根据碰撞类型不同而有明显区别，高危伤情、高发部位及高危区为非对称性分布，机动车外交通伤比车内交通伤更为严重。     

Alcohol vehicles in tests for non-immunological immediate contact reactions

In a search for vehicles that might enhance the sensitivity of human skin tests for nonimmunological immediate contact reactions, benzoic acid was tested in 17 liquid vehicles on 16 medical students using the open application test method on the upper back. The results were read visually and the change in blood flow was measured using a laser-Doppler flowmeter 20, 40 and 60 min after application of the test substances. 2-propyl alcohol (isopropanol), ethyl alcohol (ethanol), 1,2-propylene glycol and water were mixed to form alcohol, alcohol/water, alcohol/alcohol, alcohol propylene glycol and propylene glycol/water vehicles. The reactions were stronger in the alcohol/water vehicles than in the alcohols as such. The addition of 25% propylene glycol to isopropanol and ethanol had the greatest enhancing effect on the reactions. Ethanol has been the most popular liquid vehicle in tests for non-immunological immediate contact reactions, but at least with benzoic acid, stronger reactions can he elicited if alcohol/propylene glycol or alcohol/water mixture arcs used.     

Targeted alpha therapy using short-lived alpha-particles and the promise of nanobodies as targeting vehicle

ABSTRACT

Introduction: The combination of a targeted biomolecule that specifically defines the target and a radionuclide that delivers a cytotoxic payload offers a specific way to destroy cancer cells. Targeted radionuclide therapy (TRNT) aims to deliver cytotoxic radiation to cancer cells and causes minimal toxicity to surrounding healthy tissues. Recent advances using α-particle radiation emphasizes their potential to generate radiation in a highly localized and toxic manner because of their high level of ionization and short range in tissue.

Areas covered: We review the importance of targeted alpha therapy (TAT) and focus on nanobodies as potential beneficial vehicles. In recent years, nanobodies have been evaluated intensively as unique antigen-specific vehicles for molecular imaging and TRNT.

Expert opinion: We expect that the efficient targeting capacity and fast clearance of nanobodies offer a high potential for TAT. More particularly, we argue that the nanobodies’ pharmacokinetic properties match perfectly with the interesting decay properties of the short-lived α-particle emitting radionuclides Astatine-211 and Bismuth-213 and offer an interesting treatment option particularly for micrometastatic cancer and residual disease.     

Gene therapy for cystic fibrosis

After a decade of intensive research, effective gene therapy for cystic fibrosis (CF) remains an elusive goal. There have, however, been tremendous advances in our understanding of the basic processes of CF lung disease and in the development of gene therapy protocols, as reflected in the number and diversity of relevant patents issued. A selection of pertinent patents (with a bias towards those granted by the WIPO) is reviewed. Solutions to the key challenge of efficiently and safely delivering therapeutic genes to the respiratory epithelium are actively being sought. A new generation of vehicles that more effectively target cells while minimising immune responses is emerging. Vehicles and vectors that promote extended transgene persistence and expression are being developed to overcome the problems of short-term expression that characterised early clinical trials. There is ample cause for continued optimism that CF gene therapy will become a clinical reality through incremental improvements in all stages of the therapeutic process from formulation to expression.     

Characterization of drug delivery vehicles using atomic force microscopy: current status

ABSTRACT

Introduction: The field of nanomedicine, utilizing nano-sized vehicles (nanoparticles and nanofibers) for targeted local drug delivery, has a promising future. This is dependent on the ability to analyze the chemical and physical properties of these drug carriers at the nanoscale and hence atomic force microscopy (AFM), a high-resolution imaging and local force-measurement technique, is ideally suited.

Areas covered: Following a brief introduction to the technique, the review describes how AFM has been used in selected publications from 2015 to 2018 to characterize nanoparticles and nanofibers as drug delivery vehicles. These sections are ordered into areas of increasing AFM complexity: imaging/particle sizing, surface roughness/quantitative analysis of images, and analysis of force curves (to extract nanoindentation and adhesion data).

Expert opinion: AFM imaging/sizing is used extensively for the characterization of nanoparticle and nanofiber drug delivery vehicles, with surface roughness and nanomechanical/adhesion data acquisition being less common. The field is progressing into combining AFM with other techniques, notably SEM, ToF-SIMS, Raman, Confocal, and UV. Current limitations include a 50 nm resolution limit of nanoparticles imaged within live cells and AFM tip-induced activation of cytoskeleton proteins. Following drug release real-time with AFM-spectroscopic techniques and studying drug interactions on cell receptors appear to be on the horizon.     

Extracellular vesicle-mediated communication between hepatocytes and natural killer cells promotes hepatocellular tumorigenesis

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