MULTIFUNCTIONAL THERAPEUTICS USING ENGINEERED PLANT VIRUS NANOPARTICLES

纳米技术为癌症治疗带来了巨大的希望，但困难的化学问题阻碍了在疗效、消除副作用和商业化生产方面的进展。这些问题不是工程植物病毒纳米颗粒的一个因素，该纳米颗粒将用于拟议的研究。经过数百万年的进化，这种独特的病毒已经解决了生产、一致性、生物学和药代动力学问题。这种植物病毒在人类食物链中，无毒，免疫原性低。它可以通过一个简单的过程将医学显像剂和/或治疗药物装载到它的“货舱”中。这种病毒不仅可以被改造成识别和进入癌细胞，还可以靶向并在细胞结构内释放药物有效载荷，比如大多数化疗药物运作的细胞核，绕过大多数癌细胞的防御。在这个项目中，我们将实施一种新的方法来增加这些植物病毒纳米颗粒的产量。我们还将在动物模型中展示显像剂和化疗药物对耐药癌细胞和肿瘤的有效输送，为可能的第二阶段研究项目做准备，从而进一步开发最佳药物配方和用于临床试验的IND应用。

Nanotechnology holds great promise for cancer therapy, but difficult chemistry problems have impeded progress in efficacy, elimination of side effects, and commercial production. These problems are not a factor with the engineered plant virus nanoparticle that will be used in the proposed research. Through millions of years of evolution, this unique virus has solved production, uniformity, biologic, and pharmacokinetic problems. This plant virus is in the human food chain, is non toxic, and is of low immunogenicity. It can load medical imaging agents and/or therapeutic drugs into its "cargo chamber" by a simple process. The virus can not only be engineered to identify and enter cancer cells but can target and release drug payloads inside cell structures, such as the nucleus where most chemotherapy drugs operate, bypassing most cancer cell defenses. In this project, we will implement a new approach to increase production of these plant virus nanoparticles. We will also demonstrate effective delivery of imaging agents and chemotherapy drugs to drug resistant cancer cells and to tumors in an animal model, in preparation for a possible Phase II research project leading to further development of the best drug formulation and an IND application for clinical trials.