Targeted Erythrocyte Membrane-Coated Nanoparticles for the Treatment of AML

描述（由申请人提供）：急性髓性白血病（AML）是影响成人的最常见急性白血病，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，AML正逐渐成为一个重要的问题。目前的治疗方法非常密集，对患者的精神和身体都很消耗，因此需要一种更有效和高效的治疗方式。该项目的目标是利用一种新的红细胞膜包覆聚合物纳米颗粒（RBC-NP）平台来克服这一障碍。这种配方不仅可以提供化疗药物的持续递送，更重要的是，它可以专门针对白血病细胞，优先消除癌细胞。目的：1)合成并优化RBC-NPs作为体外和体内化疗药物缓释的长循环递送载体。2)合成并测试半抗体功能化红细胞膜包被的聚合纳米颗粒在体内靶向给药到人AML小鼠模型。结论：提高化疗的疗效和增加治疗药物的白血病特异性毒性在急性髓性白血病的治疗中仍然很重要。至关重要的是

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.