Engineering Virus-like Nanoparticles for Targeting the Central Nervous System

尽管已经做出了巨大的努力来开发新的策略来克服障碍，但任何治疗药物对中枢神经系统（CNS）的递送仍然是一个重大挑战。必须克服这一点，以开发对影响它的疾病（从痴呆症到运动障碍）的充分有效的治疗方法。向中枢神经系统输送治疗剂的最大限制因素是保护中枢神经系统的屏障：血脑屏障（BBB）和血脑脊液屏障（BCSFB）。我们寻求使用聚合物纳米技术来设计生物相容性和纳米尺寸的载体，这些载体能够通过不同的细胞外和生物屏障，为选择性地靶向潜在有效的治疗提供可能。我们将结合聚合物纳米技术和神经科学的最新进展，利用全身成像技术和建模方法实施实验设计和生物评估。有针对性地将治疗药物直接输送到中枢神经系统，有可能减少与当前治疗相关的衰弱性副作用，并最大限度地减少中枢神经系统退行性疾病中的神经元损伤，这两者都对患者和护理人员的终身健康和福祉具有重要意义。我们的长期目标是通过运动神经元疾病的例子来证明这项技术在临床中的潜力，团队成员拥有出色的科学和临床专业知识。我们计划将化学、物理、生物工程与临床神经科学和神经学结合起来。这将允许通过严格的工程表征将新的科学发现连接到现实世界的医学应用中。这是一个非常具有挑战性和战略性的项目。然而，实现所提出的目标对于验证一种新的生物医学输送系统非常有价值，该系统可以用于临床研究，并有可能有效治疗几种神经系统疾病。在最初的两年里，我们将把精力集中在两个特定的典型障碍上。在这些方面显示出疗效的治疗方法可能会扩展到其他常见的神经系统疾病，如帕金森病和阿尔茨海默病。到三年结束时，我们的目标是在临床前模型中确定至少一种对一种疾病/靶点具有疗效数据的给药机制。为了有效地实现这一目标，我们将在整个过程中与患者群体和公众进行接触，激发兴趣，管理期望，解决伦理和安全问题以及监管议程。为了促进任何潜在的临床评估，我们还致力于从项目的早期阶段就与药品和保健产品管理局（MHRA）、临床医生和患者团体进行接触。最后，我们将与技术转让和业务经理联系，并整合多学科培训，包括已经与我们团队建立合作关系的公司，如：Biocompatibles Ltd， Oxford BioMedica Ltd， GlaxoSmithKline和UCB Pharma。

Despite vast efforts that have been made to develop novel strategies to overcome obstacles, the delivery of any therapeutic agents to central nervous system (CNS) is still a major challenge. This must be overcome to develop fully effective treatments for conditions affecting it, from dementia to motor disorders. The most limiting factors to deliver therapeutic agents to the CNS are the barriers that protect it: the blood brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCSFB). We seek to use polymer nanotechnology to engineer biocompatible and nanometer-sized vectors that are able to pass through different extracellular and biological barriers, opening up the possibility of selectively targeting potentially effective treatments to where they are needed. We will combine recent advances in both polymer nanotechnology and neuroscience implementing experimental design and biological evaluation with whole body imaging techniques and modelling approaches. Targeted delivery of therapeutic agents direct into the CNS has the potential to cut down on debilitating side effects associated with current treatments and minimize neuronal damage in CNS degenerative disorders, both of which have major implications for life long health and well being for both patients and carers. Our long term aim is to demonstrate the potential of this technology in the clinic using the example of motor neuron disease where members of the team have excellent combined scientific and clinical expertise. We plan to interface Chemistry, Physics, Bioengineering with Clinical Neuroscience and Neurology. This will allow the bridging of novel scientific discoveries into real world medical applications through rigorous engineering characterization. This is a very challenging and strategic project. Yet, achieving the objectives presented would be very valuable in validating a novel biomedical delivery system ready for clinical studies with the potential to effectively treat several neurological disorders. In the first 2 years will focus our effort on two specific exemplar disorders. Therapies which show efficacy in those could potentially be extended for other common neurological disorders such as Parkinson's and Alzheimer's diseases. By the end of the three years, we aim to identify at least one delivery mechanism that has efficacy data for one disease/target in a preclinical model. In order to realize this effectively we will engage with patient groups and the general public throughout the process, stimulating interest, managing expectations, addressing ethical and safety concerns and the regulatory agenda. So as to facilitate any potential clinical evaluation we also aim to engage from the early stages of the programme with the Medicines and Healthcare products Regulatory Agency (MHRA), and clinicians and patient groups. Finally we will liaise with technology transfer and business managers and integrate the multidisciplinary training including companies that have already established collaborations with our team such as: Biocompatibles Ltd, Oxford BioMedica Ltd, GlaxoSmithKline, and UCB Pharma.