Viral nanoparticles as platforms for the design of novel targeted therapeutics

病毒纳米颗粒作为设计新型靶向疗法的平台

• 批准号: 8136600
• 负责人: Nicole Franziska Steinmetz
• 金额: $ 24.19万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8136600
• 关键词: Adverse effects; Animal Model; Animals; Area; Biological Availability; Blood Vessels; Cessation of life; Chemicals; Complex; Cowpea Mosaic Viruses; Development; Disease; Disorder by Site; Drug Delivery Systems; Drug Formulations; Engineering; Fullerenes; Genetic; Goals; Grant; Homing; Hybrids; Image; In Vitro; Instruction; Knowledge; Label; Learning; Life; Malignant Neoplasms; Methods; Modification; Molecular; Mosaic Viruses; Phase; Photosensitizing Agents; Pisum sativum; Plant Viruses; Positioning Attribute; Production; Property; Quality of life; Structure; Testing; Therapeutic; Tissues; Training; Virion; biomaterial compatibility; cancer therapy; chemotherapy; design; disability; hyperthermia treatment; improved; in vivo; in vivo Model; iron oxide; nanocrystal; nanodevice; nanomaterials; nanoparticle; nanostructured; new therapeutic target; novel; post-doctoral training; pre-clinical; pre-doctoral; programs; receptor; success; therapeutic target; tumor; viral nanoparticle

Targeting therapies and imaging agents specifically to areas of disease in the body, while avoiding healthy tissue, is an important goal in biomedicine. This project focuses on the utilization of the well-characterized plant virus Cowpea mosaic virus (CPMV) as a platform for the design of novel "smart" targeted therapeutics. CPMV particles are naturally occurring, monodisperse, 30 nm-sized nanoparticles. The combined biodegradability, ease of production, and tunability make CPMV an excellent candidate for such platform development. The utility of multivalent fluorescent CPMV probes for vascular imaging in live animals has been demonstrated. More recently, we showed tumor homing of specifically targeted CPMV particles in preclinical animal models. The overall goal of this proposal is the development of 'smart' 3D nanodevices that interlink targeting. Imaging, and therapy. The first goal is to explore the potential of therapeutic CPMV formulations. I will use VNPs as a template for the constrained synthesis of iron oxide nanocrystals within the capsld interior for potential applications in hyperthermia treatment. Next, I will evaluate VNP-photosensitizer (fullerene) hybrid materials for photo-activated cancer therapy. In the second goal, to combine targeting, imaging, and therapy, will fabricate highly organized, controllable, and tunable VNPs networks consisting of various different "specialized" VNPs. Such complex formulations are expected to overcome limitations of single VNPs and would allow i) targeting to several molecular receptors thus increasing tumor homing efficiency, and ii) delivery of different therapeutics, which is expected to increase therapeutic success. Cancer is a complex endeavor and i stronly believe that such multicomponent formulations may serve as promising candidates for novel targeted therapies. During my pre-doctoral training 1 have learned to tailor VNPs and to fabricate nanostructured matenals. My post-doctoral training has provided expertise in in vitro and in vivo models. This puts me in a unique position of being able to create nanomaterials, but also to study their in vivo properties.

靶向疗法和成像剂专门针对体内疾病区域，同时避免健康组织，是生物医学中的重要目标。该项目侧重于利用良好的植物病毒牛皮乳头病毒（CPMV），作为设计新型“智能”靶向疗法的平台。 CPMV颗粒是天然存在的，单分散的，30 nm大小的纳米颗粒。合并的生物降解性，易生产性和可调性使CPMV成为这种平台开发的绝佳候选者。已经证明了多价荧光CPMV探针对活动物中血管成像的实用性。最近，我们显示了临床前动物模型中特定靶向的CPMV颗粒的肿瘤归巢。 该提案的总体目标是开发“ SMART” 3D纳米版本的互联链接定位。 成像和治疗。第一个目标是探索治疗性CPMV配方的潜力。我将使用VNP作为模板，以限制CAPSLD内部内氧化铁纳米晶体的合成，以在高温治疗中进行潜在应用。接下来，我将评估用于光激活癌症治疗的VNP - 光增敏剂（富勒烯）混合材料。在第二个目标中，要结合靶向成像和治疗， 将制造由各种不同的“专业” VNP组成的高度组织，可控制和可调的VNP网络。预计这种复杂的配方将克服单个VNP的局限性，并允许i）靶向几个分子受体，从而提高肿瘤托管效率； 癌症是一项复杂的努力，我认为，这种多组分配方可能是新型靶向疗法的有前途的候选者。在我的博士前培训中，1学会了量身定制VNP并制造纳米结构的成年。我的博士后培训为体外和体内模型提供了专业知识。这使我处于能够创建纳米材料的独特位置，也可以研究其体内特性。