NANOPHOTOSENSITIZERS FOR REGENERATIVE PHOTOTHERAPY

用于再生光疗的纳米光敏剂

基本信息

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
项目类别：
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

项目摘要

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.

抽象的关于纳米医学的兴奋源于纳米科学在解决挑战方面的潜在应用医疗问题。结合fen座的骨髓环境（BME）和高度特异的金属 - 骨骼的结合基质，杀死癌症的纳米颗粒（NP）非常适合克服电流实现骨骼病变持久疗法的障碍。多种用于将药物输送到BME的NP 并成功证明了功效。但是，纳米颗粒也有效作为治疗剂，然而，该特征在骨骼病变的治疗中不足。最近，我们开发了放射性核素刺激的疗法，以利用Cerenkov辐射的相互作用发射放射性核素以刺激光敏剂的活性氧的产生。这这些药物的结合将允许治疗各种疾病，而不会限制组织深度影响基于光的疗法。在此提案中，我们将应用此概念来破坏具有基质细胞的癌细胞。两种细胞类型的失活都将增强治疗反应。因此，我们将利用1。无机纳米颗粒来无活性的保护性基质细胞和2。纳米叶胶体为BME提供高有效载荷。研究将使用体内和体外模型进行癌症。成像将用于监测治疗反应。这项研究完成后，我们将开发用于癌症治疗和成像的新纳米植物。和骨骼病变。