Development of Tumor-Targeted Pegylated Colloidal Gold *

描述（由申请人提供）： 目前，可切除实体瘤的一线治疗最常见的是手术，然后是化疗和/或放疗方案。不幸的是，这种策略经常因为复发或转移性疾病而失败。为了改变这种模式，新的癌症疗法必须提供多方面的治疗方法，以在手术切除之前破坏实体瘤中存在的异质性肿瘤细胞群。目前的提案旨在在聚乙二醇化胶体金纳米颗粒平台（cAu）上开发这种肿瘤靶向纳米疗法，该平台旨在向实体瘤提供有效抗癌药物的组合。开发的第一种药物（命名为CYT-0691）积极靶向和隔离实体瘤中的人肿瘤坏死因子α（TNF），同时避免网状内皮系统（RES）的摄取和清除。该药物由TNF和巯基化聚乙二醇（一种RES避免分子）组成，它们作为单个分子共价结合到26 nm cAu纳米颗粒的表面。该提案旨在使用与聚乙二醇化cAu纳米颗粒结合的TNF作为新的组合癌症纳米疗法家族的核心。这些新的纳米疗法将被组装在聚乙二醇化cAu的单个颗粒上，并被设计用于递送TNF和与TNF对实体瘤的已知作用协同的第二种治疗剂。 所提出的cAu纳米药物的多价性质将要求我们进一步了解纳米颗粒平台以及推定的治疗剂与cAu纳米颗粒表面的相互作用。为了应对这一挑战，Cytlmmune组建了一个多学科专家团队，以解决使聚乙二醇化cAu纳米颗粒成为开发肿瘤靶向纳米治疗药物的平台技术的基本和应用挑战。每个团队成员的专业知识将用于解决cAu纳米颗粒的表面结合化学，cAu结合药物的合成和表征以及每个新的聚乙二醇化cAu纳米颗粒载体的生物学表征的具体问题。Cytlmmune的合作者包括弗吉尼亚理工大学的大卫金森博士，来自克拉克森大学的Dan Goia博士，卡内基研究所地球物理实验室的Viktor Struzhkin博士和Andrew Steele博士，以及布法罗大学化学系的Paras Prasad博士和Haridas Pudavar博士。

DESCRIPTION (provided by applicant): Currently, first-line treatment of resectable solid tumors most commonly involves surgery followed by a regimen of chemotherapy and/or radiation. Unfortunately, this strategy often fails because of recurrent or metastatic disease. To change this paradigm, new cancer therapies must deliver multifaceted therapeutics to destroy the heterogeneous population of tumor cells present within solid tumors prior to surgical removal. The current proposal seeks to develop such tumor-targeted nanotherapies on a pegylated colloidal gold nanoparticle platform (cAu) designed to deliver a combination of potent anti-cancer drugs to solid tumors. The first drug developed (designated CYT-0691) actively targets and sequesters human tumor necrosis factor alpha (TNF) in solid tumors while avoiding uptake and clearance by the reticuloendothelial system (RES). The drug is comprised of TNF and thiolated polyethylene glycol (an RES avoidance molecule) that are covalently bound, as individual molecules, to the surface of 26 nm cAu nanoparticles. This proposal seeks to use TNF bound to pegylated cAu nanoparticles as the core of a family of new combinational cancer nanotherapies. These new nanotherapies will be assembled on a single particle of pegylated cAu and are designed to deliver both TNF and a second therapeutic that synergizes with the known actions of TNF on solid tumors. The multivalent nature of the proposed cAu nanodrugs will require us to further our current understanding of the nanoparticle platform and the interaction of the putative therapeutics with the cAu nanoparticle's surface. To meet this challenge, Cytlmmune has assembled a multidisciplinary team of experts to address the basic and applied challenges of making pegylated cAu nanoparticles a platform technology for developing tumor-targeted nanotherapeutics. The expertise of each team member will be brought to bear in addressing specific issues of surface binding chemistries to cAu nanoparticles, the synthesis and characterization of the cAu bound drugs, and the biologic characterization of each new pegylated cAu nanoparticle vector. Cytlmmune's collaborators include Dr. David Kingson of Virginia Tech., Dr. Dan Goia from Clarkson University, Drs. Viktor Struzhkin and Andrew Steele of the Geophysical Laboratory of the Carnegie Institute, and Drs. Paras Prasad and Haridas Pudavar of the Department of Chemistry at the University of Buffalo.