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Enzyme-catalyzed self-propelling particles: Applications for drug delivery to solid tumors.

机译:酶催化的自推进颗粒:将药物递送至实体瘤的应用。

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摘要

Cancer is one of the oldest diseases known to mankind, and remains one of the most complex ailments to diagnose, treat and manage. Considerable scientific research has been conducted to understand the mechanisms that govern cancer and to discover therapeutics, and yet this class of diseases still accounts for a lion's share of the global health burden. An emerging consensus over the past decade has been the importance of the 'tumor microenvironment' in the progression of the disease. The many transport barriers imposed by the microenvironment renders even potent drugs inefficient and makes them poor therapeutic candidates. In this context, nanotechnology has emerged as a powerful resource, since it operates at length scales commonly found in biology, and also provides the opportunity to engineer nanoparticle-based drug carrier systems which incorporate the desirable traits of an efficient therapeutic.;The work presented here is based on the idea that nano-scale objects can be designed to use the tumor microenvironment to improve their transport and distribution. Janus Particles are a special class of nanoparticles that exhibit some form of physical and/or chemical asymmetry on their surface. Of special interest is a class of Janus particles called 'Janus motors', which are designed specifically to use this asymmetry to convert chemical energy to mechanical energy and achieve 'self-propulsive' motion.;We report the design and synthesis of silica Janus motors via the Pickering emulsion method, using a naturally occurring enzyme, catalase, which catalyzes the decomposition of hydrogen peroxide into water and oxygen. Enzymes offer many benefits over conventional metal catalysts which are commonly used in Janus motors. They typically exhibit higher catalytic efficiencies which can also be tuned by adjusting environmental conditions such as pH, temperature, chemical activators/inhibitors and so on. Particle tracking experiments on the particles allowed us to probe the mechanisms by which these particles achieve propulsion. Since the eventual goal of this work is to test these particles as drug delivery agents, an in vitro 3D tumor spheroid model of breast cancer has also been developed using a metastatic breast cancer cell line (MDA-MB-231) and Collagen Type I as the extra-cellular matrix.;This model was used to investigate the expression of an important cell surface biomarker, the transferrin receptor (TfR), which has been used previously to design particles for targeted therapy to tumors. The work presented here lays the foundation for the use of Janus motors as drug carriers which incorporate both an active enzyme as well as a targeting ligand such as Transferrin that can potentially overcome the transport barriers faced by conventional systems, and lead to improved therapies.
机译:癌症是人类已知的最古老的疾病之一,并且仍然是诊断,治疗和管理最复杂的疾病之一。为了理解控制癌症的机制并发现治疗方法,已经进行了相当多的科学研究,但是这类疾病仍然占全球健康负担的最大份额。在过去的十年中,新兴的共识是“肿瘤微环境”在疾病进展中的重要性。微环境施加的许多运输障碍甚至使有效药物效率低下,并使它们成为不良的治疗候选物。在这种情况下,纳米技术已经成为一种强大的资源,因为它以生物学中常见的长度规模运作,并且还提供了机会来设计基于纳米粒子的药物载体系统,该系统结合了有效治疗剂的理想特性。这是基于这样的想法,即可以设计纳米尺度的物体以利用肿瘤微环境来改善其运输和分布。 Janus粒子是一类特殊的纳米粒子,在其表面上表现出某种形式的物理和/或化学不对称性。特别令人关注的是一类称为“ Janus电机”的Janus颗粒,它们专门设计用于利用这种不对称性将化学能转换为机械能并实现“自推进”运动。;我们报告了二氧化硅Janus电机的设计和合成通过Pickering乳液法,使用天然存在的酶过氧化氢酶,该酶催化过氧化氢分解为水和氧气。与Janus电机中常用的常规金属催化剂相比,酶具有许多优势。它们通常表现出较高的催化效率,也可以通过调节环境条件(例如pH值,温度,化学活化剂/抑制剂等)来调节。对粒子的粒子跟踪实验使我们能够探究这些粒子实现推进的机制。由于这项工作的最终目标是测试这些颗粒是否作为药物递送剂,因此还使用转移性乳腺癌细胞系(MDA-MB-231)和I型胶原作为乳腺癌的体外3D肿瘤球体模型进行了开发。该模型用于研究重要细胞表面生物标志物转铁蛋白受体(TfR)的表达,该标志物先前已用于设计用于肿瘤靶向治疗的颗粒。此处介绍的工作为使用Janus电机作为药物载体奠定了基础,该载体结合了活性酶和靶向配体(例如转铁蛋白),可以潜在地克服常规系统面临的运输障碍,并导致改进的疗法。

著录项

  • 作者

    Rao, Suhas.;

  • 作者单位

    Rensselaer Polytechnic Institute.;

  • 授予单位 Rensselaer Polytechnic Institute.;
  • 学科 Chemical engineering.
  • 学位 Ph.D.
  • 年度 2014
  • 页码 120 p.
  • 总页数 120
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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