Multi-functional Nanocarrier against Canine Lymphoma

抗犬淋巴瘤的多功能纳米载体

• 批准号: 8611720
• 负责人: KIT S LAM
• 金额: $ 49.92万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2016-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8611720
• 关键词: Abraxane; Acids; Adverse drug effect; Animals; Avastin; B-Cell Lymphomas; B-Lymphocytes; Biodistribution; Bortezomib; Breast; Cancer Patient; Canis familiaris; Cell surface; Charge; Combination Drug Therapy; Companions; Cytotoxic agent; DNA; Development; Disseminated Malignant Neoplasm; Doxorubicin; Drug Formulations; Drug Kinetics; Drug Targeting; Exhibits; FDA approved; Gefitinib; Image; In Vitro; Intercalating Agents; Label; Lead; Libraries; Ligands; Lymphoma; Malignant Neoplasms; Maximum Tolerated Dose; Methods; Micelles; Microscopy; Modeling; Mus; Non-Hodgkin' s Lymphoma; Organ; Ovarian; Paclitaxel; Particle Size; Patients; Pharmaceutical Preparations; Phase; Phase I Clinical Trials; Polymers; Property; Proteasome Inhibitor; Radioisotopes; Radiolabeled; Rattus; Reporting; Research; Shapes; Site; Solid Neoplasm; Surface; Therapeutic; Therapeutic Agents; Toxic effect; Transgenic Mice; Treatment Efficacy; United States; Velcade; Vincristine; Xenograft Model; analog; base; cancer type; cell type; combinatorial; design; in vivo; inhibitor/antagonist; multicatalytic endopeptidase complex; nano; nanocarrier; nanoformulation; nanoparticle; nanotherapeutic; nanotherapy; neoplastic cell; novel; optical imaging; public health relevance; radiotracer; screening; theranostics; tumor; uptake

DESCRIPTION (provided by applicant): The multifunctional micelle-based targeting nanotherapeutics to be developed in this project offer an opportunity to deliver high concentration of cytotoxic drugs (e.g. doxorubicine), molecularly targeted drugs (e.g. bortezomib [Velcade(R)], a proteosome inhibitor) as well as therapeutic radionuclides such as 131I to the tumor sites while sparing normal organs, thus greatly enhance the anti-tumor effects and lessen the systemic side effects of these drugs. As a result, we expect patients with advanced non- Hodgkin lymphoma (both T- and B-cell type) or solid tumors will benefit from such novel nanotherapies. In addition, such multifunctional nanoplatform can also be used as tumor imaging agents. Our nanotherapeutic platform is unique and comprised of oligocholic acid based micelles with drugs loaded inside and cancer targeting ligands decorating the micelle surface. We believe the addition of LLP2A, a lymphoma targeting ligand, to the nanotherapeutics can facilitate the intracellular delivery of the nanocarrier to the tumor cells in vivo and therefore will greatly enhance their anti-tumor efficacies. In this proposed research, biodistribution properties (imaging) and therapeutic efficacies of such targeting nanoparticles will be evaluated in both transgenic mouse lymphoma models and spontaneous canine lymphoma. This research will lead to the development of more efficacious and less toxic multifunctional targeting nanoformulations of bortexomib (a proteasome inhibitor), doxorubicin (a DNA intercalate), and therapeutic radionuclide 131I, all of which are expected to be useful in the treatment of many cancer types including non-Hodgkin lymphoma (NHL). If successful, this therapeutic approach can be applied to many other cancer types as well and therefore will have a great impact in the survival of cancer patients in the United States and around the world.

描述（由申请人提供）：本项目将开发的多功能基于胶束的靶向纳米治疗药物提供了输送高浓度细胞毒性药物（例如阿霉素）、分子靶向药物（例如硼替佐米 [Velcade(R)]、一种蛋白酶体）的机会。抑制剂）以及131I等治疗性放射性核素到达肿瘤部位，同时不伤害正常器官，从而大大增强抗肿瘤作用作用并减轻这些药物的全身副作用。因此，我们预计晚期非霍奇金淋巴瘤（T 细胞型和 B 细胞型）或实体瘤患者将从此类新型纳米疗法中受益。此外，这种多功能纳米平台还可以用作肿瘤成像剂。 我们的纳米治疗平台是独特的，由寡胆酸基胶束组成，内部装有药物，胶束表面装饰有癌症靶向配体。我们相信，在纳米治疗药物中添加淋巴瘤靶向配体LLP2A可以促进纳米载体在体内递送至肿瘤细胞，从而大大增强其抗肿瘤功效。在这项拟议的研究中，将在转基因小鼠淋巴瘤模型和自发性犬淋巴瘤模型中评估此类靶向纳米粒子的生物分布特性（成像）和治疗效果。 这项研究将导致开发更有效、毒性更低的多功能靶向纳米制剂，包括硼替索米（一种蛋白酶体抑制剂）、阿霉素（一种 DNA 嵌入物）和治疗性放射性核素 131I，所有这些药物预计将可用于治疗许多癌症类型包括非霍奇金淋巴瘤（NHL）。如果成功，这种治疗方法也可以应用于许多其他癌症类型，因此将对美国和世界各地癌症患者的生存产生巨大影响。