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  • 刊频： Quarterly
  • NLM标题： Bioeng Transl Med
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共147条结果
  • 1.

    【2hr】Engineering nanoparticles to overcome barriers to immunotherapy

    包量

    机译 工程纳米粒子克服免疫疗法的障碍
    摘要：Advances in immunotherapy have led to the development of a variety of promising therapeutics, including small molecules, proteins and peptides, monoclonal antibodies, and cellular therapies. Despite this wealth of new therapeutics, the efficacy of immunotherapy has been limited by challenges in targeted delivery and controlled release, that is, spatial and temporal control on delivery. Particulate carriers, especially nanoparticles have been widely studied in drug delivery and vaccine research and are being increasingly investigated as vehicles to deliver immunotherapies. Nanoparticle‐mediated drug delivery could provide several benefits, including control of biodistribution and transport kinetics, the potential for site‐specific targeting, immunogenicity, tracking capability using medical imaging, and multitherapeutic loading. There are also a unique set of challenges, which include nonspecific uptake by phagocytic cells, off‐target biodistribution, permeation through tissue (transport limitation), nonspecific immune‐activation, and poor control over intracellular localization. This review highlights the importance of understanding the relationship between a nanoparticle's size, shape, charge, ligand density and elasticity to its vascular transport, biodistribution, cellular internalization, and immunogenicity. For the design of an effective immunotherapy, we highlight the importance of selecting a nanoparticle's physical characteristics (e.g., size, shape, elasticity) and its surface functionalization (e.g., chemical or polymer modifications, targeting or tissue‐penetrating peptides) with consideration of its reactivity to the targeted microenvironment (e.g., targeted cell types, use of stimuli‐sensitive biomaterials, immunogenicity). Applications of this rational nanoparticle design process in vaccine development and cancer immunotherapy are discussed.
  • 2.

    【2hr】Evaluation of receptor‐ligand mechanisms of dual‐targeted particles to an inflamed endothelium

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    机译 评价双靶标颗粒对内皮发炎的受体配体机制
    摘要：Vascular‐targeted carriers (VTCs) are designed as leukocyte mimics, decorated with ligands that target leukocyte adhesion molecules (LAMs) and facilitate adhesion to diseased endothelium. VTCs require different design considerations than other targeted particle therapies; adhesion of VTCs in regions with dynamic blood flow requires multiple ligand‐receptor (LR) pairs that provide particle adhesion and disease specificity. Despite the ultimate goal of leukocyte mimicry, the specificity of multiple LAM‐targeted VTCs remains poorly understood, especially in physiological environments. Here, we investigate particle binding to an inflamed mesentery via intravital microscopy using a series of particles with well‐controlled ligand properties. We find that the total number of sites of a single ligand can drive particle adhesion to the endothelium, however, combining ligands that target multiple LR pairs provides a more effective approach. Combining sites of sialyl Lewis A (sLeA) and anti‐intercellular adhesion molecule‐1 (aICAM), two adhesive molecules, resulted in ∼3–7‐fold increase of adherent particles at the endothelium over single‐ligand particles. At a constant total ligand density, a particle with a ratio of 75% sLeA: 25% aICAM resulted in more than 3‐fold increase over all over other ligand ratios tested in our in vivo model. Combined with in vivo and in silico data, we find the best dual‐ligand design of a particle is heavily dependent on the surface expression of the endothelial cells, producing superior adhesion with more particle ligand for the lesser‐expressed receptor. These results establish the importance of considering LR‐kinetics in intelligent VTC ligand design for future therapeutics.
  • 3.

    【2hr】Nanoparticles in the clinic

    包量

    机译 临床中的纳米颗粒
    摘要：Nanoparticle/microparticle‐based drug delivery systems for systemic (i.e., intravenous) applications have significant advantages over their nonformulated and free drug counterparts. For example, nanoparticle systems are capable of delivering therapeutics and treating areas of the body that other delivery systems cannot reach. As such, nanoparticle drug delivery and imaging systems are one of the most investigated systems in preclinical and clinical settings. Here, we will highlight the diversity of nanoparticle types, the key advantages these systems have over their free drug counterparts, and discuss their overall potential in influencing clinical care. In particular, we will focus on current clinical trials for nanoparticle formulations that have yet to be clinically approved. Additional emphasis will be on clinically approved nanoparticle systems, both for their currently approved indications and their use in active clinical trials. Finally, we will discuss many of the often overlooked biological, technological, and study design challenges that impact the clinical success of nanoparticle delivery systems.
  • 4.

    【2hr】Letter from the Editor

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    机译 编者的信
    摘要：
  • 5.

    【2hr】Letter from AIChE President

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    机译 AIChE总裁的信
    摘要：
  • 6.

    【2hr】Biomimetic strategies for targeted nanoparticle delivery

    包量

    机译 靶向纳米颗粒的仿生策略
    摘要：Nanoparticle‐based drug delivery and imaging platforms have become increasingly popular over the past several decades. Among different design parameters that can affect their performance, the incorporation of targeting functionality onto nanoparticle surfaces has been a widely studied subject. Targeted formulations have the ability to improve efficacy and function by positively modulating tissue localization. Many methods exist for creating targeted nanoformulations, including the use of custom biomolecules such as antibodies or aptamers. More recently, a great amount of focus has been placed on biomimetic targeting strategies that leverage targeting interactions found directly in nature. Such strategies, which have been painstakingly selected over time by the process of evolution to maximize functionality, oftentimes enable scientists to forgo the specialized discovery processes associated with many traditional ligands and help to accelerate development of novel nanoparticle formulations. In this review, we categorize and discuss in‐depth recent works in this growing field of bioinspired research.
  • 7.

    【2hr】Dose enhancement and cytotoxicity of gold nanoparticles in colon cancer cells when irradiated with kilo‐ and mega‐voltage radiation

    包量

    机译 千伏和兆伏电压辐照在结肠癌细胞中金纳米颗粒的剂量增强和细胞毒性
    摘要：Despite major advances in the field of radiotherapy, healthy tissue damage continues to constrain the dose that can be prescribed in cancer therapy. Gold nanoparticles (GNPs) have been proposed as a solution to minimize radiation‐associated toxicities by enhancing the radiation dose delivered locally to tumor cells. In the current study, we investigated the application of third‐generation GNPs in two‐dimensional (2D) and three‐dimensional (3D) cell cultures and whether there is synergy between the nanoparticles and kilo‐ or mega‐voltage radiation to cause augmented cytotoxicity. The 10‐nm GNPs were found to be nontoxic in both 2D and 3D in vitro cultures of colon cancer cells at concentrations of up to 10–25 µg/ml. There was a significant increase in cell survival fraction reduction following exposure to 1 Gy of kilo‐voltage (18.3%) and 2 Gy of mega‐voltage (35.3%) radiation when the cells were incubated with 50 µg/ml of GNPs. The biocompatibility of the GNPs combined with their substantial synergy with radiation encourages further investigations into their application in targeted cancer treatment.
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