Targeted Erythrocyte Membrane-Coated Nanoparticles for the Treatment of AML

描述(申请人提供)：急性髓系白血病(AML)是影响成人的最常见的急性白血病，2012年估计有13,780例新病例和10,200例死亡。54%的患者确诊年龄在65岁或以上，AML的发病率随着年龄的增长而增加。因此，随着人口老龄化，急性髓细胞白血病正成为一个日益重要的问题。目前的治疗非常密集，对患者的精神和体力都有消耗，这就需要一种更有效和更高效的治疗模式。本项目的目标是利用一种新型的红细胞膜包裹聚合物纳米颗粒(RBC-NP)平台来克服这一障碍。这一制剂不仅将提供化疗药物的持续输送，更重要的是将专门针对白血病细胞并优先消除癌细胞。目的：1)合成并优化RBC-NPs作为缓释化疗药物的长循环载体，用于治疗AML的体内外研究。2)合成半抗体功能化红细胞膜包裹的聚合物纳米粒，用于体内靶向给药至人急性髓系白血病小鼠模型。结论：提高化疗疗效，增加治疗药物的白血病特异性毒性在急性髓细胞白血病的治疗中仍具有重要意义。这是至关重要的 有效治疗患者，同时将不良反应降至最低，从而提高他们的生活质量。目前AML的治疗方法包括治疗窗口窄、血液消除半衰期短的药物。假设通过延长化疗药物的循环半衰期和控制其释放，可以更可靠地控制血药浓度，从而更有效地治疗AML。

DESCRIPTION (provided by applicant): Acute myeloid leukemia (AML) is the most common acute leukemia that affects adults, with an estimated 13,780 new cases and 10,200 deaths in 2012. 54% of patients are diagnosed at 65 years or older, with the incidence of AML increasing with age. Thus, AML is becoming a progressively important issue as the population ages. Current therapies are extremely intensive and both mentally and physically draining on the patient, necessitating the need for a more effective and efficient mode of treatment. The objective of this project is to overcome this hurdle using a novel red blood cell membrane-coated polymer nanoparticle (RBC-NP) platform. This formulation will not only offer sustained delivery of chemotherapy drugs, but more importantly will specifically target leukemia cells and preferentially eliminate the cancerous cells. Aims: 1) To synthesize and optimize RBC-NPs as long-circulating delivery vehicles for sustained release of chemotherapy drugs to treat AML in vitro and in vivo. 2) To synthesize and test half-antibody functionalized RBC membrane-coated polymeric nanoparticles for targeted drug delivery in vivo to a human AML model in mice. Conclusion: Improving the therapeutic efficacy of chemotherapy and increasing leukemia-specific toxicity of therapeutic drugs remains important in the treatment of AML. It is critical to effectively treat patients while inducing minimal adverse side effects, thereby improving their quality of life. Current treatment methods for AML involve drugs with narrow therapeutic windows and short blood elimination half-lives. It is hypothesized that by extending the circulation half-life of chemotherapeutic drugs and controlling their release, the plasma drug concentration can be more reliably controlled, thereby more effectually treating AML.