SBIR Phase II: Targeted Nanoparticle Delivery Agent for Treatment of Adult Leukemia

这个小企业创新研究第二阶段项目将开发靶向纳米颗粒递送系统，能够优先向肿瘤细胞递送常规细胞毒素。虽然治疗性纳米颗粒已经被引入临床实践（Abraxane（TM）和Doxil（TM）），并且其他的正在开发中，但是还没有开发出显示肿瘤靶向特异性（与增加的亲和力相反）或递送多种治疗剂（无论是常规的细胞毒性剂还是靶向剂）的纳米颗粒。该项目的假设是，通过高度模块化和合成稳健的纳米颗粒靶向递送癌症治疗可以改善治疗反应，同时最大限度地减少几乎任何癌症治疗的全身毒性作用。在I期研究中，这种方法的创新性通过使用我们专有的纳米颗粒药物显着降低成人白血病转基因小鼠模型的肿瘤负荷来证明。该II期提案的技术目标旨在改进和优化治疗成人白血病的纳米颗粒制剂。该II期提案将完成纳米颗粒递送载体的临床前研究的关键阶段，以预期向FDA申请这种新药的IND状态。该项目更广泛的影响/商业潜力为增加纳米材料的价值提供了一个很好的机会。2010年，纳米技术支持的药物递送疗法的更广泛市场刚刚超过10亿美元，预计到2021年将迅速增长到1360亿美元，同期的复合年增长率（CAGR）估计为49.96%。仅在美国，估计就有274，930人患有白血病。2011年，估计有44，600人（25，320名男性和19，280名女性）被诊断患有白血病，其中成人人数是儿童和青少年的10倍。同样在2011年，21,780名已经患有白血病的人预计将死于这种疾病。美国癌症协会预测2012年的数字甚至更高，估计美国将有47，150人被诊断患有白血病，大约23，540名患者将死于白血病。这里提出的纳米颗粒递送系统通过展示治疗剂有效地递送到白血病细胞，在科学水平上很好地推进了药物递送领域。结合有效的肿瘤输送，这种技术可以促进高效，？个性化？目前常规全身治疗无法实现的癌症治疗。

This Small Business Innovation Research Phase II project will develop targeted nanoparticle delivery systems capable of delivering conventional cytotoxics preferentially to tumor cells. While therapeutic nanoparticles have been introduced into clinical practice (Abraxane(TM) and Doxil(TM)) and others are in development, none have been developed that show tumor target specificity (as opposed to increased affinity) or deliver multiple therapeutic agents (whether conventional cytotoxic or targeted agents). The hypothesizias underlying this project is that targeted delivery of cancer therapy via highly modular and synthetically robust nanoparticles can improve therapeutic response while minimizing systemic toxic effects of therapy for virtually any cancer. In the Phase I study, the innovation of this approach was demonstrated by dramatically reducing the tumor burden in a transgenic mouse model of adult leukemia with our proprietary nanoparticle agents. The technical objectives in this Phase II proposal are designed to refine and optimize the nanoparticle formulation to treat adult leukemia. This Phase II proposal will enable the completion a critical phase of the preclinical studies for the nanoparticle delivery vehicle to anticipate applying for IND status for this new drug with the FDA. The broader impact/commercial potential of this project offers a great opportunity to add value to nanomaterials. The broader market for nanotech-enabled drug-delivery therapeutics was just over $1 billion in 2010 and is projected to mushroom to $136 billion by the year 2021, with a compound annual growth rate (CAGR) estimated at 49.96% over the same period. Within the U.S. alone, there are an estimated 274,930 people living with leukemia. In 2011, it is estimated that 44,600 people (25,320 men and 19,280 women) were diagnosed with leukemia, including 10 times as many adults as children and adolescents. Also in 2011, 21,780 of those already afflicted with leukemia were expected to die from the disease. The American Cancer Society projects even higher figures for 2012, estimating that 47,150 people in the U.S. will be diagnosed with leukemia and that approximately 23,540 patients will die from it. The nanoparticle delivery system proposed here is well positioned to advance the drug delivery field on a scientific level by demonstrating efficient delivery of therapeutics to leukemia cells. Combined with effective tumor delivery this technology could facilitate highly effective, ?personalized? cancer therapy that is not currently possible with routine systemic therapy.