NANOPHOTOSENSITIZERS FOR REGENERATIVE PHOTOTHERAPY

用于再生光疗的纳米光敏剂

• 批准号: 10596383
• 负责人: Samuel Achilefu
• 金额: $ 73.42万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-04 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10596383
• 关键词: Adrenal Cortex Hormones; Affect; Award; Back; Binding; Bone Marrow; Bone Matrix; Bortezomib; CAR T cell therapy; Cancer Model; Cell Death; Cells; Cessation of life; Chemoresistance; Cherenkov Radiation; Combination Drug Therapy; Combined Modality Therapy; Complex; Coupled; Data; Dexamethasone; Disease; Disease remission; Disease-Free Survival; Dose; Drug Combinations; Drug resistance; Environment; Fibroblasts; Funding; Glucose Transporter; Grant; Image; Immunomodulators; Immunosuppression; Injections; Lesion; Ligands; Light; Malignant Bone Neoplasm; Malignant Neoplasms; Medical; Metals; Methods; Molecular; Monitor; Monoclonal Antibodies; Multiple Myeloma; Nanotechnology; Natural regeneration; Osteoclasts; Osteolysis; Outcome; Pathogenesis; Pathway interactions; Patients; Pharmaceutical Preparations; Phenotype; Photosensitizing Agents; Phototherapy; Plasma Cells; Process; Production; Progression-Free Survivals; Property; Proteasome Inhibitor; Publications; Quality of life; Radioisotopes; Radiolabeled; Radiopharmaceuticals; Reactive Oxygen Species; Relapse; Resistance; Seminal; Source; Stromal Cells; Testing; Therapeutic; Therapeutic Agents; Tissues; Toxic effect; Transferrin; Treatment outcome; Tumor Burden; Ultraviolet Rays; base; bone; cancer cell; cancer imaging; cancer therapy; cell type; clinical translation; cytotoxic; field study; fluorodeoxyglucose; improved; in vitro Model; in vivo; lenalidomide; mouse model; nano; nanoliposome; nanomedicine; nanoparticle; nanoscience; nanotechnology platform; nanotherapy; novel; prevent; regenerative; side effect; spatiotemporal; stem; success; titanium dioxide; titanocene; treatment response; tumor; tumor growth

ABSTRACT The excitement about nanomedicine stems from the potential application of nanoscience to solve challenging medical problems. Coupled with the fenestrated bone marrow environment (BME) and the highly specific metal- binding matrix of the bone, cancer-killing nanoparticles (NPs) are uniquely suited to overcome current impediments to achieving durable therapy for bone lesions. A variety of NPs used to deliver drugs to the BME and has successfully demonstrated efficacy. However, nanoparticles are also effective as therapeutic agents, yet this feature is underutilized in the treatment of bone lesions. Recently, we developed radionuclide stimulated therapy that leverages the interaction of Cerenkov radiation emitting radionuclides to stimulate the production of reactive oxygen species from photosensitizers. The combination of these drugs will allow the treatment of diverse diseases without the limitation of tissue depth that affects light-based therapies. In this proposal, we will apply this concept to disrupt the protective interaction of cancer cells with stromal cells. The inactivation of both cell types will enhance treatment response. Accordingly, we will utilize 1. inorganic nanoparticles to inactive the protective stromal cells, and 2. nanoliposomes to deliver high payloads to the BME. The studies will be conducted with in vivo and in vitro models of cancer. Imaging will be used to monitor treatment response. At the completion of this study, we would develop new nanoplatforms for the treatment and imaging of cancer and bone lesions.

摘要 对纳米医学的兴奋源于纳米科学的潜在应用，以解决具有挑战性的 医疗问题。再加上开窗骨髓环境（BME）和高度特异性的金属- 结合骨基质，癌症杀伤纳米颗粒（NPs）是唯一适合克服电流 这是实现骨病变持久治疗的障碍。用于将药物递送至BME的各种NP 并已成功证明其有效性。然而，纳米颗粒作为治疗剂也是有效的， 然而，在骨损伤的治疗中，该特征未得到充分利用。 最近，我们开发了利用切伦科夫辐射相互作用的放射性核素刺激疗法， 发射放射性核素以刺激光敏剂产生活性氧物质。的 这些药物的组合将允许治疗多种疾病而不受组织深度的限制， 影响光疗法在本提案中，我们将应用这一概念来破坏 癌细胞和基质细胞两种细胞类型的失活将增强治疗反应。 因此，我们将使用1。无机纳米颗粒使保护性基质细胞失活，和2. 纳米脂质体以向BME递送高有效载荷。研究将采用体内和体外模型进行 癌症。成像将用于监测治疗反应。 在这项研究完成后，我们将开发新的纳米平台，用于癌症的治疗和成像。 和骨损伤。