Viral nanoparticles as platforms for the design of novel targeted therapeutics

靶向治疗和成像剂专门针对身体疾病区域，同时避免健康组织，是生物医学的一个重要目标。该项目的重点是利用具有良好特征的植物病毒豇豆花叶病毒（CPMV）作为设计新型“智能”靶向治疗药物的平台。 CPMV颗粒是天然存在的、单分散的、30 nm大小的纳米颗粒。结合生物降解性，易于生产和可调性使CPMV成为这种平台开发的优秀候选者。多价荧光CPMV探针用于活体动物血管成像的实用性已经得到证实。最近，我们在临床前动物模型中显示了特异性靶向CPMV颗粒的肿瘤归巢。 该提案的总体目标是开发相互关联的靶向“智能”3D纳米器件。 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，在高温治疗中的潜在应用capsld内部的氧化铁纳米晶体的约束合成。接下来，我将评估VNP-光敏剂（富勒烯）混合材料用于光活化癌症治疗。在第二个目标中，结合联合收割机靶向、成像和治疗， 将制造高度有组织的，可控的，可调的VNPs网络组成的各种不同的“专业”VNPs。预期此类复合制剂克服单一VNP的限制，并且将允许i）靶向若干分子受体，从而增加肿瘤归巢效率，和ii）递送不同的治疗剂，这预期增加治疗成功。 癌症是一项复杂的奋进，我坚信这种多组分制剂可能成为新靶向治疗的有希望的候选药物。在我的博士前培训期间，我学会了定制VNPs和制造纳米结构材料。我的博士后培训提供了体外和体内模型的专业知识。这使我处于一个独特的位置，能够创造纳米材料，但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.