Targeted Erythrocyte Membrane-Coated Nanoparticles for the Treatment of AML

靶向红细胞膜包被的纳米颗粒用于治疗 AML

• 批准号: 8715271
• 负责人: Brian T Luk
• 金额: $ 3.43万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8715271
• 关键词: Acute Myelocytic Leukemia; Acute leukemia; Address; Adult; Adverse effects; Affect; Age; Antibodies; Biodistribution; Biomimetics; Blast Cell; Blood; Blood Circulation; Body Weight; CD47 gene; Cancerous; Cell membrane; Cells; Cessation of life; Chemistry; Clinic; Daunorubicin; Diagnosis; Dose; Drug Carriers; Drug Controls; Drug Delivery Systems; Drug Formulations; Drug usage; Erythrocyte Membrane; Erythrocytes; Half-Life; Human; IL3RA gene; Immune; Immune response; In Vitro; Incidence; Interleukin-3; Intravenous; Kinetics; Leukemic Cell; Ligands; Membrane Proteins; Methods; Modality; Modeling; Modification; Molecular Conformation; Mus; Nature; Normal Cell; Patients; Pharmaceutical Preparations; Phase I Clinical Trials; Plasma; Polymers; Population; Process; Production; Property; Proteins; Quality of life; Relative (related person); Stem cells; Surface; System; Taxes; Techniques; Testing; Therapeutic; Time; Tissues; Toxic effect; Translations; Treatment Efficacy; Treatment Protocols; Work; base; bench to bedside; chemotherapy; cytotoxicity; design; dosage; improved; in vivo; killings; leukemia; leukemic stem cell; nanoparticle; nanotherapeutic; new technology; novel; overexpression; public health relevance; receptor; research study; residence; therapeutic target

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.

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例新发病例和10，200例死亡。54%的患者在65岁或以上被诊断，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正在成为一个日益重要的问题。目前的治疗是非常密集的，在精神和身体上对患者的排水，需要一个更有效和高效的治疗模式。该项目的目标是使用新型红细胞膜包被聚合物纳米颗粒（RBC-NP）平台克服这一障碍。这种制剂不仅提供化疗药物的持续递送，更重要的是将特异性靶向白血病细胞并优先消除癌细胞。目的：1）合成和优化RBC-NPs作为用于化疗药物的缓释的长循环递送载体，以在体外和体内治疗AML。2)合成并测试半抗体功能化RBC膜包被的聚合物纳米颗粒，用于体内靶向药物递送至小鼠中的人AML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AML的治疗中仍然很重要。至关重要 有效地治疗患者，同时引起最小的不良副作用，从而提高他们的生活质量。目前AML的治疗方法涉及具有窄治疗窗和短血液消除半衰期的药物。据推测，通过延长化疗药物的循环半衰期并控制其释放，可以更可靠地控制血浆药物浓度，从而更有效地治疗AML。