Intravascular Delivery of Nanoclusters for Treatment of Deep-Seated Cancers with Magnetic Hyperthermia

血管内输送纳米簇用于磁热疗治疗深部癌症

• 批准号: 10555274
• 负责人: Oleh Taratula
• 金额: $ 50.39万
• 依托单位: OREGON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-03-01 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10555274
• 关键词: Address; Animal Model; Animals; Biodistribution; Cell Death Induction; Chemotherapy and/or radiation; Clinical; Clinical Research; Cobalt; Data; Desmoplastic; Disseminated Malignant Neoplasm; Dose; Encapsulated; Exposure to; Goals; Heating; Human; Hyperthermia; Implant; In Situ; Injections; Intravenous; Ions; Magnetic nanoparticles; Magnetism; Malignant Neoplasms; Malignant neoplasm of ovary; Malignant neoplasm of pancreas; Manganese; Mediating; Metals; Modality; Modeling; Mus; Neoplasm Metastasis; Pancreatic Ductal Adenocarcinoma; Peptides; Predisposition; Primary Neoplasm; Rattus; Reproducibility; Research; Research Personnel; Rodent; Shapes; Site; Surface; Technology; Temperature; Testing; Therapeutic; Tissues; Toxic effect; Treatment Efficacy; Xenograft procedure; Zinc; anticancer research; biomaterial compatibility; cancer cell; cancer therapy; chemotherapy; clinical translation; clinically relevant; efficacy evaluation; improved; intraperitoneal; intravenous administration; intravenous injection; invention; iron oxide; iron oxide nanoparticle; magnetic field; multidisciplinary; nanocluster; nanomedicine; nanoparticle; nanoparticle delivery; nanopolymer; novel; ovarian neoplasm; pancreatic cancer cells; pancreatic cancer model; pancreatic neoplasm; preclinical study; preservation; subcutaneous; targeted delivery; translational potential; tumor; tumor growth; tumor specificity; validation studies

Project Summary Magnetic hyperthermia is a highly promising therapeutic modality for treatment of various cancers. It is based on the concept that magnetic nanoparticles delivered to cancer tumors can generate heat after exposure to a non-invasive external alternating magnetic field (AMF). Many preclinical and clinical studies have validated the significant potential of nanoparticle-mediated hyperthermia to either kill cancer cells directly or enhance their susceptibility to radiation and chemotherapy. Despite its promising potential, magnetic hyperthermia is currently limited to treatment of localized and relatively accessible tumors, because the required therapeutic temperatures above 42 0C can only be achieved by direct intratumoral injection of conventional iron oxide nanoparticles. To realize the true potential of magnetic hyperthermia as a therapy for deep-seated primary and metastatic tumors, it is necessary to develop nanoparticles that can efficiently accumulate at tumor sites following systemic administration and generate desirable intratumoral temperatures upon exposure to AMF. A multidisciplinary team of investigators with complementary expertise in nanomedicine, magnetic hyperthermia, and cancer research will develop novel nanoparticles with high heating capacity that efficiently accumulate in primary and metastatic tumors following a single systemic injection and generate desirable intratumoral temperatures upon exposure to AMF. The research team will capitalize on its recent invention of magnetic nanoclusters consisting of hexagonal-shaped nanoheaters encapsulated in polymeric nanoparticles. Preliminary studies validated that these nanoclusters are safe, efficiently accumulate in subcutaneous cancer tumors after intravenous injection, elevate the intratumoral temperature to 44 0C in the presence of AMF, and significantly inhibit tumor growth. To advance this technology, the first major goal of this project is to optimize the developed nanoclusters for targeted delivery to ovarian and pancreatic cancer tumors by modifying their surface with the LHRH peptide. The second goal is to confirm, in rodents with metastatic ovarian cancer and orthotopic pancreas cancer, that the nanoclusters are efficient in increasing temperature of deep-seated primary and metastatic tumors. The third goal is to validate therapeutic efficacy of the nanocluster-mediated hyperthermia alone and in combination with chemotherapy in these animal models. These goals will be addressed with the following Specific Aims: 1. Optimize translational potential and tumor-targeted delivery of the developed nanoclusters. 2. Evaluate optimized magnetic nanoclusters in mice with human metastatic ovarian cancer. 3. Assess optimized magnetic nanoclusters in an orthotopic model of pancreatic cancer. At the completion of this project, the team expects to produce strong evidence that the optimized nanoclusters will efficiently accumulate in metastatic and deep-seated tumors following intravascular injection, produce the required intratumoral temperature, and significantly reduce the size of ovarian and pancreatic tumors. The long term goal is to develop a novel magnetic hyperthermia-based treatment for the tested tumors.

项目总结