Biofunctional Polymers for Intracellular Drug Delivery

用于细胞内药物输送的生物功能聚合物

• 批准号: 7466737
• 负责人: Patrick S. Stayton
• 金额: $ 50.2万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-19 至 2012-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7466737
• 关键词: Animal Model; Antibodies; Antisense Oligonucleotides; Architecture; Area; Biodistribution; Biological Assay; Biological Response Modifier Therapy; Blood Circulation; Burkitt Lymphoma; Cells; Charge; Chemicals; Chronic Lymphocytic Leukemia; Chronic Myeloid Leukemia; Clinical; Clinical Treatment; Clinical Trials; Cultured Cells; DNA; Dependence; Development; Disruption; Drug Delivery Systems; Drug Formulations; Drug Kinetics; Drug Stability; Elements; Equilibrium; Erythrocytes; Exhibits; Follicular Lymphoma; Gene Silencing; Gene Targeting; Grant; Hematologic Agents; Hemolysis; Ions; Label; Lymphoma; Lysosomes; Malignant Neoplasms; Measurement; Membrane; Messenger RNA; Methods; Modeling; Mus; Non-Hodgkin' s Lymphoma; Nuclear; Nucleic Acids; Nude Mice; Oncogenes; Organism; Pathogenesis; Pathologic; Penetration; Pharmaceutical Preparations; Polymerase Chain Reaction; Polymers; Property; Protein Family; Proteins; Public Health; Radio; Range; Recycling; Research; Research Personnel; Small Interfering RNA; System; Technology; Therapeutic; Time; Tissues; Translations; Treatment Efficacy; Virus; Western Blotting; Xenograft procedure; anti-cancer therapeutic; base; copolymer; cytotoxic; design; extracellular; fusion gene; in vivo; leukemia/lymphoma; membrane activity; neoplastic; novel; octadecaneuropeptide; pH gradient; research clinical testing; response; size; success; therapeutic target

DESCRIPTION (provided by applicant): The objective of this proposal is to develop approaches to enhance the delivery of nucleic acid based therapeutics to intracellular targets in Non-Hodgkin Lymphoma (NHL) cells. The project will utilize novel pH-sensitive "smart polymer" based carriers to penetrate the endosomal barrier that limits entry to the cytoplasmic and nuclear compartments where antisense-ODN and siRNA exert their gene silencing effects. We believe that siRNA and AS-ODN have great potential for the treatment of NHL and hypothesize that improvement in delivery methods will facilitate their success in the clinical setting. PUBLIC HEALTH REVELANCE This project aims to develop new drug delivery systems for biomolecular drugs that must reach intracellular targets for efficacy. Biotherapeutics such as siRNA, antisense oligonucleotides (ODN), and proteins have significant therapeutic potential, but effectively formulating and delivering them remains a widely recognized challenge. Here we will develop smart polymeric carriers for siRNA drugs, and such carriers might be used widely for other DNA, RNA, and protein drugs.

描述（由申请人提供）：该提案的目的是开发方法，以增强非霍奇金淋巴瘤（NHL）细胞中细胞内靶标的基于核酸的疗法的递送。该项目将利用基于新型的pH敏感的“智能聚合物”载体穿透内体屏障，该障碍限制了进入细胞质和核室，而反义 - odn和siRNA发挥其基因沉默作用。我们认为，siRNA和AS-ODN具有巨大的治疗NHL的潜力，并假设改善输送方法将有助于其在临床环境中的成功。公共卫生的启示该项目旨在开发新的药物输送系统，以实现效果的细胞内靶标。诸如siRNA，反义寡核苷酸（ODN）和蛋白质之类的生物治疗剂具有显着的治疗潜力，但有效制定和递送它们仍然是一个广泛认可的挑战。在这里，我们将开发用于siRNA药物的智能聚合物载体，并且此类载体可以广泛用于其他DNA，RNA和蛋白质药物。