SBIR Phase II: Scaling up the Synthesis of Novel Poly(ethylene glycol) Based Dendrimers for Targeted Drug Delivery Applications

SBIR 第二阶段：扩大用于靶向药物输送应用的新型聚乙二醇树枝状聚合物的合成

• 批准号: 1353531
• 负责人: Attila Gergely
• 金额: $ 74.97万
• 依托单位: PolyInsight, LLC
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-04-15 至 2016-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1353531&HistoricalAwards=false
• 关键词: SBIR; Phase; II; Scaling; up

This Small Business Innovation Research Phase II project is aimed at the design and manufacture of agents useful for the diagnosis and treatment of breast and other cancers. The primary product is a novel water-soluble molecule constructed from poly(ethylene glycol) (or PEG), containing multiple arms with folate groups as well as a diagnostic agent. The folate groups will target cancer cells preferentially over healthy cells and the fluorescent diagnostic agent will allow effective breast cancer diagnosis. This targeting molecule differs from currently available materials in that the length and number of the PEG arms as well as the attachment of folate groups can be very carefully and reproducibly controlled, addressing a critical weakness with previous multifunctional devices. The precision synthesis steps are catalyzed by an enzyme, leading to very pure products. Currently three folate-targeted diagnostic molecules are in Phase III clinical trials, but all are based on small molecules and a single folate targeting group. The advantage of a polymer-based device with multiple folate groups will be a longer circulation time in the body with more effective targeting of cancer cells. The broader impact/commercial potential of this project is significant since by 2020 approximately 18.2 million Americans will be diagnosed with cancer. Breast cancer is the most frequently diagnosed cancer in both white and African-American women. One in eight American women develops breast cancer, and a new patient is diagnosed in every three minutes. Chemotherapy has many side effects such as hair loss and nausea, and requires extended patient care. Specific targeting is a significant advantage for diagnostic and chemotherapeutic agents. When a drug is delivered directly to the cancer cell to kill it, the collateral damage of healthy cells is minimized. New delivery devices are badly needed for cancer diagnosis and therapy, and if successful this project will provide both a new diagnostic agent as well as a platform technology for additional products. Another impact of this project is the use of an enzyme-catalyzed green manufacturing process which minimizes wasteful by-products. In the longer term, the market potential will be significant as the technology is adapted to specific diagnostic and therapeutic products.

这个小企业创新研究第二阶段项目旨在设计和制造用于诊断和治疗乳腺癌和其他癌症的药物。主要产物是由聚（乙二醇）（或PEG）构建的新型水溶性分子，包含具有叶酸基团的多个臂以及诊断剂。叶酸基团将优先靶向癌细胞而不是健康细胞，并且荧光诊断剂将允许有效的乳腺癌诊断。这种靶向分子与目前可用的材料的不同之处在于，PEG臂的长度和数量以及叶酸基团的连接可以非常仔细和可重复地控制，解决了先前多功能装置的关键弱点。精确的合成步骤由酶催化，从而产生非常纯的产品。目前，三种叶酸靶向诊断分子正在进行III期临床试验，但它们都是基于小分子和单一的叶酸靶向组。具有多个叶酸基团的基于聚合物的装置的优点是在体内循环时间更长，更有效地靶向癌细胞。该项目的更广泛影响/商业潜力是显著的，因为到2020年，大约1820万美国人将被诊断患有癌症。 乳腺癌是白色和非洲裔美国妇女中最常诊断的癌症。八分之一的美国女性患乳腺癌，每三分钟就有一名新患者被诊断出来。化疗有许多副作用，如脱发和恶心，需要长期的病人护理。 特异性靶向是诊断剂和化疗剂的显著优点。当药物被直接递送到癌细胞以杀死它时，健康细胞的附带损害被最小化。癌症诊断和治疗迫切需要新的输送设备，如果成功，该项目将为其他产品提供新的诊断试剂和平台技术。该项目的另一个影响是使用酶催化的绿色制造工艺，最大限度地减少了浪费的副产品。从长远来看，市场潜力将是巨大的，因为该技术适用于特定的诊断和治疗产品。