USING VIRAL NANOPARTICLES TO TARGET CANCER

描述(申请人提供)：纳米技术为癌症的早期发现和治疗带来了巨大的希望。不需要活检、手术或其他侵入性技术就可以检测和跟踪癌症的发生和发展，这应该会导致更低的成本和更高的生活质量。这项提议的目标是开发病毒纳米颗粒(VNPs)作为体内肿瘤靶向和显像剂结合的平台。我们的多学科团队结合了分子生物学、结构、化学和体内生物学来解决这个问题。在这项提案中，我们将研究两种特性良好的病毒：植物病毒，豌豆花叶病毒(CPMV)；以及昆虫病毒，鸡舍病毒(FHV)。合作研究实验室开发的关于FHV和CPMV的结构、功能、组装、基因组包装、化学附着和体内生物利用度的积累知识，使这些病毒成为此类平台开发的理想候选者。我们将测试肿瘤特异性VNPs在体内外攻击肿瘤细胞的能力，并研究VNPs被细胞摄取的机制。我们还将在颗粒内包装抗肿瘤化合物和抑制基因，以促进肿瘤的破坏。最后，我们将测试我们的VNPs在体内检测和摧毁肿瘤的能力。这些研究将对改进的肿瘤靶向和成像纳米技术的发展做出重大贡献。

DESCRIPTION (provided by applicant): Nanotechnology holds great promise for the early detection and treatment of cancer. The ability to both detect and follow the initiation and progression of cancer without biopsy, surgery, or other invasive techniques should lead to lower costs and higher quality of life. The goal of this proposal is to develop viral nanoparticles (VNPs) as platforms for combination tumor targeting and imaging agents in vivo. Our multidisciplinary team combines molecular biology, structure, chemistry and in vivo biology to attack this problem. In this proposal we will study two well-characterized viruses: a plant virus, cowpea mosaic virus (CPMV); and an insect virus, flockhouse virus (FHV). The accumulated knowledge of the structure, function, assembly, genome packaging, chemical attachment, and in vivo bioavailability of FHV and CPMV, developed in the co-investigators' laboratories, makes these viruses ideal candidates for such platform development. We will test the ability of tumor-specific VNPs to attack tumor cells in vitro and in vivo, and study mechanisms of uptake of VNPs into cells. We will also package anti-tumor compounds and inhibitory genes inside the particles to facilitate tumor destruction. Finally we will test the ability of our VNPs to detect and destroy tumors in vivo. These studies will make a significant contribution to the development of improved tumor targeting and imaging nanotechnologies.