Engineering Virus-like Nanoparticles for Targeting the Central Nervous System

用于靶向中枢神经系统的工程病毒样纳米颗粒

• 批准号: EP/G062137/1
• 负责人: Giuseppe Battaglia
• 金额: $ 270.88万
• 依托单位: University of Sheffield
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2009
• 资助国家: 英国
• 起止时间: 2009 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FG062137%2F1
• 关键词: Engineering; Virus; like; Nanoparticles; Targeting

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.

尽管已经做出了巨大的努力来开发新的策略来克服障碍，但将任何治疗剂递送至中枢神经系统（CNS）仍然是一个重大挑战。必须克服这一点，才能开发出完全有效的治疗方法来治疗从痴呆到运动障碍等影响它的疾病。将治疗剂递送至CNS的最大限制因素是保护它的屏障：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，从而开辟了选择性地将潜在有效的治疗靶向到需要的地方的可能性。我们将结合联合收割机在两个聚合物纳米技术和神经科学实施实验设计和生物评价与全身成像技术和建模方法的最新进展。将治疗剂直接靶向递送到CNS中具有减少与当前治疗相关的使人衰弱的副作用和使CNS退行性疾病中的神经元损伤最小化的潜力，这两者对于患者和护理者的终身健康和幸福都具有重大意义。我们的长期目标是以运动神经元疾病为例，展示这项技术在临床上的潜力，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病学相结合。这将允许通过严格的工程表征将新颖的科学发现桥接到真实的世界医学应用中。这是一个非常具有挑战性和战略性的项目。然而，实现所提出的目标将是非常有价值的，在验证一种新的生物医学输送系统准备用于临床研究，有可能有效地治疗几种神经系统疾病。在最初的2年里，我们将集中精力在两个特定的典型疾病。在这些疾病中显示出疗效的疗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具有一种疾病/靶点疗效数据的递送机制。为了有效地实现这一目标，我们将在整个过程中与患者团体和公众接触，激发兴趣，管理期望，解决道德和安全问题以及监管议程。为了促进任何潜在的临床评估，我们还旨在从该计划的早期阶段与药品和保健产品监管局（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，包括已经与我们的团队建立合作关系的公司，如：Biocompatibles Ltd，Oxford BioMedica Ltd，GlaxoSmithKline和UCB Pharma。

项目成果

A Multiscale Study of Phosphorylcholine Driven Cellular Phenotypic Targeting.

磷酸胆碱驱动的细胞表型靶向的多尺度研究。

• DOI: 10.1021/acscentsci.2c00146
• 发表时间: 2022-07-27
• 期刊: ACS CENTRAL SCIENCE
• 影响因子: 18.2
• 作者: Acosta-Gutierrez, Silvia;Matias, Diana;Avila-Olias, Milagros;Gouveia, Virginia M.;Scarpa, Edoardo;Forth, Joe;Contini, Claudia;Duro-Castano, Aroa;Rizzello, Loris;Battaglia, Giuseppe
• 通讯作者: Battaglia, Giuseppe

Exploiting Endocytosis for Nanomedicines

• DOI: 10.1101/cshperspect.a016980
• 发表时间: 2013-11-01
• 期刊: COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY
• 影响因子: 7.2
• 作者: Akinc, Akin;Battaglia, Giuseppe
• 通讯作者: Battaglia, Giuseppe

Tailoring Macromolecular Expression at Polymersome Surfaces

• DOI: 10.1002/adfm.200900201
• 发表时间: 2009-09-23
• 期刊: ADVANCED FUNCTIONAL MATERIALS
• 影响因子: 19
• 作者: Blanazs, Adam;Massignani, Marzia;Ryan, Anthony J.
• 通讯作者: Ryan, Anthony J.

Bottom-up Evolution from Disks to High-Genus Polymersomes

从盘到高属聚合物体的自下而上进化

• DOI: 10.26434/chemrxiv.6108467
• 发表时间: 2018
• 作者: Battaglia G

On the design of precision nanomedicines

精密纳米药物的设计

• DOI: 10.26434/chemrxiv.5647969
• 发表时间: 2019
• 作者: Battaglia G