NANOPHOTOSENSITIZERS FOR REGENERATIVE PHOTOTHERAPY

用于再生光疗的纳米光敏剂

基本信息

批准号：
10317997
负责人：
Samuel Achilefu
金额：
$ 70.85万
依托单位：
WASHINGTON UNIVERSITY
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 2022-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10317997
关键词：
Adrenal Cortex Hormones Affect Award Binding Biological Biological Availability Bone Marrow Bone Matrix Bortezomib CAR T cell therapy Carbon Cell Death Cells Cherenkov Radiation Clinical Treatment Clonal Expansion Combined Modality Therapy Complement Complex Coupled Data Disease Disease-Free Survival Dose Drug Delivery Systems Drug resistance Encapsulated Engineering Environment Event Exhibits Fluorine Fracture Funding Glucose Transporter Grant Hematologic Neoplasms Hematopoietic Neoplasms High Dose Chemotherapy Human Hypoxia Image Immunomodulators Immunosuppression Intervention Intravenous Lesion Light Lipids Liver Lung Malignant - descriptor Malignant Bone Neoplasm Malignant Neoplasms Mediating Medical Medicine Metals Methods Molecular Monoclonal Antibodies Multiple Myeloma Nanotechnology Natural regeneration Nucleic Acids Organelles Osteolysis Outcome Oxidation-Reduction Oxygen Pathway interactions Patients Penetration Peripheral Nervous System Diseases Pharmaceutical Preparations Photosensitizing Agents Phototherapy Plasma Process Prodrugs Production Progression-Free Survivals Property Proteasome Inhibitor Proteins Quality of life Quantum Dots Radioisotopes Radiolabeled Radiopharmaceuticals Reactive Oxygen Species Relapse Research Residual Tumors Resistance Science Seminal Signal Pathway Site Solid Neoplasm Source Spleen Stromal Cells Supporting Cell Surface Technology Testing Therapeutic Therapeutic Effect Thrombocytopenia Tissues Toxic effect Transducers Transferrin Treatment outcome Ultraviolet Rays absorption base bone cancer cell cancer imaging cancer therapy chemotherapy clinically translatable cytotoxic effective therapy field study fluorodeoxyglucose human disease imaging agent improved in vivo nano nanomaterials nanomedicine nanoparticle nanoparticle delivery nanoscale nanoscience nanotechnology platform nanotherapy neurotoxicity novel prevent regenerative relapse patients side effect spatiotemporal stem systemic toxicity therapy outcome titanium dioxide titanocene treatment response treatment strategy tumor tumor growth

项目摘要

ABSTRACT The excitement about nanomedicine stems from the potential application of nanoscience to solve challenging medical problems. Inorganic nanoparticles (iNPs) exhibit unique properties that favor their diverse application in medicine, engineering, science, and technology. The large surface-to-volume ratio of these iNPs provides sites for the attachment of multiple drugs or imaging agents for therapy and imaging of diverse human diseases. Further conjugation of biological entities, such as proteins, nucleic acids, and lipids, confers specific targeting of these iNPs to desired tissues in vivo. Recent studies have shown that the intrinsic properties of some iNPs can be harnessed for therapeutic outcomes. Still, spontaneous stimulation of intrinsic therapeutic effects through interactions of the NPs with intracellular organelles, proteins, or molecular processes is difficult to control, leading to significant off-target toxicity. An alternative therapeutic approach is to transform some iNPs into nanoscale energy transducers. Quantum dots, upconversion NPs, carbon nanomaterials, and photocatalytic NPs are some nanoscale energy transducers that have shown promise in the treatment of human diseases. The excellent redox properties of these nanophotosensitizers offer high spatiotemporal control and precision phototherapy upon absorption of light. Two major limitations of current phototherapeutic interventions are the limited penetration of light used to activate the photosensitizers, which confines therapy to shallow lesions, and the frequent reliance on molecular oxygen to generate cytotoxic reactive oxygen species, a condition that precludes the effective treatment under the hypoxic conditions found in many solid and hematologic tumors. 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 spatiotemporal therapeutic effects of these interactions allow the treatment of diverse diseases without tissue depth limitation that affects light-based therapies. Supported by new concepts grounded in robust preliminary data, we propose to (1) explore new nanostrategies to overcome the impediment to delivering NPs to tumors, (2) disrupt the protective interactions of cancer with stromal cells to enhance treatment response, and (3) exert sustainable therapeutic effect via multidimensional combination therapy to achieve disease-free survival. At the completion of this study, we would develop new nanoplatforms for the treatment and imaging of cancer and bone lesions.

抽象的人们对纳米医学的兴奋源于纳米科学解决问题的潜在应用具有挑战性的医疗问题。无机纳米颗粒 (iNP) 表现出独特的特性，有利于其多样化在医学、工程、科学和技术中的应用。这些 iNP 具有较大的表面积与体积比提供多种药物或成像剂的附着位点，用于不同人类的治疗和成像疾病。生物实体（例如蛋白质、核酸和脂质）的进一步缀合赋予了特定的将这些 iNP 靶向体内所需组织。最近的研究表明，某些物质的内在特性 iNP 可用于治疗结果。尽管如此，内在治疗效果的自发刺激通过纳米粒子与细胞内细胞器、蛋白质或分子过程的相互作用很难控制，导致显着的脱靶毒性。另一种治疗方法是转化一些 iNP 转化为纳米级能量转换器。量子点、上转换纳米颗粒、碳纳米材料和光催化纳米粒子是一些纳米级能量转换器，在治疗人类疾病方面显示出了前景。这这些纳米光敏剂优异的氧化还原特性提供了高时空控制和精度吸收光后进行光疗。当前光疗干预措施的两个主要限制是用于激活光敏剂的光穿透有限，这将治疗限制在浅层病变处，以及经常依赖分子氧产生细胞毒性活性氧，这种情况在许多实体瘤和血液肿瘤的缺氧条件下，阻碍了有效治疗。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。这这些相互作用的时空治疗作用允许在没有组织的情况下治疗多种疾病影响光疗法的深度限制。受到基于稳健初步的新概念的支持根据数据，我们建议（1）探索新的纳米策略来克服向肿瘤递送纳米粒子的障碍， (2) 破坏癌症与基质细胞的保护性相互作用，以增强治疗反应，(3) 发挥作用通过多维联合治疗实现可持续治疗效果，实现无病生存。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平台和骨病变。