Viral nanoparticles as platforms for the design of novel targeted therapeutics

在避开健康组织的同时，专门针对身体疾病区域的治疗和显像剂，是生物医学的一个重要目标。本项目致力于利用具有良好特性的植物病毒--豌豆花叶病毒(CPMV)作为平台，设计新型的“智能”靶向治疗药物。 CPMV颗粒是自然产生的、单分散的、30纳米大小的纳米颗粒。CPMV的生物可降解性、生产简便性和可调性使其成为此类平台开发的极佳候选者。多价荧光CPMV探针在活体动物血管成像中的应用已被证明。最近，我们在临床前动物模型中显示了特定靶向CPMV颗粒的肿瘤归巢。 这项提议的总体目标是开发能够相互链接靶标的“智能”3D纳米设备。 成像和治疗。第一个目标是探索治疗性CPMV制剂的潜力。我将使用VNPs作为模板，在胶囊内部限制合成氧化铁纳米晶体，以用于热疗的潜在应用。接下来，我将评估用于光激活癌症治疗的VNP-光敏剂(富勒烯)杂化材料。在第二个目标中，将靶向、成像和治疗相结合， 将构建高度组织、可控和可调的VNPs网络，由各种不同的“专门”VNPs组成。这种复杂的制剂有望克服单一VNPs的局限性，并将允许i)靶向多个分子受体从而提高肿瘤归巢效率，以及ii)提供不同的治疗方法，这有望增加治疗成功。 癌症是一项复杂的工作，我坚信这样的多组分配方可能会成为新的靶向治疗的有前途的候选药物。在我的博士前培训期间，我学会了量身定做VNPs和制造纳米结构的金属膜。我的博士后培训提供了体外和体内模型方面的专业知识。这让我处于一个独特的位置，能够创造纳米材料，也可以研究它们的体内特性。

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.