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

这个小型企业创新研究二期项目将开发靶向纳米颗粒递送系统，能够将传统的细胞毒素优先递送到肿瘤细胞。虽然治疗性纳米颗粒已经被引入临床实践（Abraxane（TM）和Doxil(TM)），其他纳米颗粒也正在开发中，但没有一种纳米颗粒显示出肿瘤靶向特异性（与增加亲和力相反）或提供多种治疗药物（无论是传统的细胞毒性药物还是靶向药物）。该项目的假设是，通过高度模块化和合成强大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治疗对几乎任何癌症的全身毒性作用。在I期研究中，该方法的创新被证明是通过使用我们专有的纳米颗粒药物显著减少了成人白血病转基因小鼠模型的肿瘤负荷。该二期计划的技术目标是改进和优化纳米颗粒配方，以治疗成人白血病。该II期提案将使纳米颗粒递送载体临床前研究的关键阶段得以完成，从而为该新药向FDA申请IND状态做好准备。该项目的广泛影响/商业潜力为纳米材料的增值提供了一个很好的机会。2010年，纳米技术给药疗法的广阔市场刚刚超过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274930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，其中成人的人数是儿童和青少年的10倍。同样在2011年，预计已有21780名白血病患者将死于这种疾病。美国癌症协会（American Cancer Society）对2012年的预测甚至更高，估计美国将有47150人被诊断出患有白血病，约23540名患者将死于白血病。本文提出的纳米颗粒给药系统通过展示治疗药物对白血病细胞的有效递送，很好地定位于在科学水平上推进药物递送领域。结合有效的肿瘤递送，这项技术可以促进高效、个性化的肿瘤递送。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.