Nanovalve Platform: Targeted, Controlled, Release of Anticancer Drugs

Nanovalve平台：靶向、可控、释放抗癌药物

• 批准号: 8206804
• 负责人: Andre Elias Nel
• 金额: $ 39.36万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-01-01 至 2014-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8206804
• 关键词: Adriamycin PFS; Antineoplastic Agents; Apoptosis; California; Camptothecin; Cancer cell line; Cell Death; Cell Line; Cell membrane; Cells; Chemotherapy-Oncologic Procedure; Confocal Microscopy; Constitution; Coumarins; DNA Binding; DNA Binding Agent; Doxorubicin; Drug Delivery Systems; Dyes; Environment; Folate; Goals; Human; Injection of therapeutic agent; Institutes; Investigation; Label; Laboratories; Ligands; Light; Malignant Epithelial Cell; Molecular Machines; Mus; Natural Killer Cells; Nude Mice; Paclitaxel; Performance; Pharmaceutical Preparations; Principal Investigator; Propidium Diiodide; Proteins; Pseudorotaxanes; Research; Research Personnel; Silicon Dioxide; Site; Solid; Solutions; Stimulus; Structure; Surface; System; Testing; Universities; alpha benzopyrone; aqueous; azobenzene; cancer cell; cancer therapy; capsule; chemotherapeutic agent; controlled release; design; improved; improved functioning; light effects; mouse model; nano; nanomachine; nanoparticle; nanosystems; novel; novel strategies; operation; particle; public health relevance; response; skills; subcutaneous; targeted delivery; tissue culture; tumor; tumor growth; tumor xenograft; uptake

DESCRIPTION (provided by applicant): The goal of the proposed research is to use mesoporous silica nanoparticles with bistable molecular machines to deliver anticancer drugs. The active structures are nanomachines that consist of a solid silica support that contains designed pores, and moving parts that trap drug molecules and release them from the pores only on external command or under desired conditions. Two types of machines, nanoimpellers that actively eject molecules from the pores, and nanovalves that block and unblock the entrances to the pores will be used to control the delivery of drugs. The assembly is coated with molecules or proteins that target the capsules to cancer cells. The first specific aim is to improve and optimize nanomachines (a pH activated valve, a light-activated impeller, a light activated valve) that were developed in the principal investigators laboratories, modify the surfaces for specific cancer cell targeting, and optimize their performance. The second aim will demonstrate operation of the machines in human cancer cells by studying the release of a fluorescent DNA binding agent and to demonstrate the delivery and on-demand release of anticancer drugs (paclitaxel, camptothecin and doxorubicin) in human carcinoma cell lines. Finally, the third aim will evaluate and utilize the nanoparticles in human tumor xenografts grown in athymic mice. By having the valves open only in a tumor, it will be possible to achieve release of anticancer drugs only at specific sites or in response to specific stimuli, thus eliminating unwanted effects on non-cancerous cells. The nano valves and impellers allow sophisticated control of the delivery of the drugs. PUBLIC HEALTH RELEVANCE: Nanoparticles that contain pores controlled by molecular machines will be used to release anticancer drugs under control. The result of the research will be a novel system for cancer chemotherapy that eliminates unwanted effects on non-cancerous cells.

描述（由申请人提供）：拟议的研究的目的是将带有可动分子机器的介孔二氧化硅纳米颗粒提供抗癌药物。活性结构是纳米机器，由固体二氧化硅支撑组成，其中包含设计的毛孔，并仅在外部指挥或所需条件下将其捕获药物分子并将其从毛孔中释放出来。两种类型的机器，积极从孔中射出分子的纳米粉碎机，以及阻塞和解除孔隙入口的纳米卵巢将用于控制药物的递送。组件涂有靶向胶囊靶向癌细胞的分子或蛋白质。第一个具体目的是改善和优化纳米机器（pH活化阀，光激活的叶轮，光活化阀），这些纳米机是在主要研究人员实验室中开发的，修改了特定癌细胞靶向的表面，并优化其性能。第二个目的将通过研究荧光DNA结合剂的释放，并证明人类癌细胞细胞系中抗癌药物（紫杉醇，甲虫和阿霉素）抗癌药物的递送和点播释放和点播抗癌药物（紫杉醇，camptothecin和adobiubicin），证明了机器在人类癌细胞中的运行。最后，第三个目标将评估和利用纳米颗粒在无胸腺小鼠中生长的人类肿瘤异种移植物中。通过仅在肿瘤中打开瓣膜，只能在特定部位或对特定刺激的响应中释放抗癌药物，从而消除对非癌细胞的不良影响。纳米阀和叶轮可以复杂地控制药物的输送。 公共卫生相关性：包含由分子机器控制的孔的纳米颗粒将用于释放受到控制的抗癌药物。该研究的结果将是一种新型的癌症化学疗法系统，可消除对非癌细胞的不良影响。