NANOPHOTOSENSITIZERS FOR REGENERATIVE PHOTOTHERAPY

用于再生光疗的纳米光敏剂

• 批准号: 10461894
• 负责人: Samuel Achilefu
• 金额: $ 71.76万
• 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/10461894
• 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; Dimensions; 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; Infection; Intervention; Intravenous; Lesion; Light; Lipids; Liver; Lung; Malignant - descriptor; Malignant Neoplasms; Mediating; Medical; Medicine; Metals; Methods; Modality; Molecular; Monoclonal Antibodies; Multiple Myeloma; Nanotechnology; Natural regeneration; Nucleic Acids; Organelles; Osteolysis; Outcome; Oxidation-Reduction; Oxygen; Paper; Patients; Penetration; Peripheral Nervous System Diseases; Pharmaceutical Preparations; Photosensitizing Agents; Phototherapy; Plasma Cells; Process; Prodrugs; Production; Progression-Free Survivals; Property; Proteasome Inhibitor; Proteins; Quality of life; Quantum Dots; Radioisotopes; Radiolabeled; Radiopharmaceuticals; Reactive Oxygen Species; Relapse; Research; Residual Neoplasm; 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; bone; cancer cell; cancer imaging; cancer therapy; cell dimension; chemotherapy; clinical translation; 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; novel therapeutic intervention; prevent; regenerative; relapse patients; side effect; spatiotemporal; stem; systemic toxicity; therapy outcome; titanium dioxide; titanocene; treatment response; treatment strategy; tumor; tumor growth

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 纳米医学的兴奋源于纳米科学的潜在应用解决 具有挑战性的医疗问题。无机纳米颗粒（INP）具有独特的特性，有利于它们的多样性 在医学，工程，科学和技术中的应用。这些INP的较大的地表与体积比 提供用于附着多种药物或成像剂的地点，以治疗和成像多样化的人类 疾病。生物实体的进一步结合，例如蛋白质，核酸和脂质，赋予了特定的特定 将这些INP靶向体内所需的组织。最近的研究表明，某些的内在特性 INP可以用于治疗结果。尽管如此，自发刺激内在的治疗效果 通过NP与细胞内细胞器的相互作用，蛋白质或分子过程很难很难 控制，导致明显的脱靶毒性。另一种治疗方法是改变一些INP 进入纳米级能量传感器。量子点，上转换NP，碳纳米材料和光催化 NP是一些纳米级能量传感器，在治疗人类疾病方面已经有望。这 这些纳米光增敏剂的出色氧化还原特性可提供高时空控制和精度 吸收光后光疗。当前光质干预措施的两个主要局限性是 用于激活光敏剂的光渗透有限，将治疗限制在浅病变中，并且 经常依赖分子氧产生细胞毒性活性氧的氧气，这种情况是 在许多固体和血液学肿瘤中发现的缺氧条件下，排除了有效治疗。 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 这些相互作用的时空治疗作用允许治疗没有组织的各种疾病 影响基于光的疗法的深度限制。由以强大的初步为基础的新概念支持 数据，我们建议（1）探索新的纳米构造，以克服向肿瘤传递NP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）施加 可持续的治疗作用通过多维联合疗法实现无疾病生存。 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植物。 和骨骼病变。

项目成果

Quantitative tumor depth determination using dual wavelength excitation fluorescence.

• DOI: 10.1364/boe.468059
• 发表时间: 2022-08
• 期刊: Biomedical optics express
• 影响因子: 3.4
• 作者: Christine M. O’Brien;Kevin Bishop;Haini Zhang;Xiao Xu;L. Shmuylovich;Elizabeth Conley;Karen Nwosu;K. Duncan;Suman B Mondal;G. Sudlow;S. Achilefu

Nanoparticle T cell engagers for the treatment of acute myeloid leukemia.

• DOI: 10.18632/oncotarget.28054
• 发表时间: 2021-09-14
• 期刊: Oncotarget
• 作者: Alhallak K;Sun J;Muz B;Jeske A;Yavner J;Bash H;Park C;Lubben B;Adebayo O;Achilefu S;DiPersio JF;Azab AK
• 通讯作者: Azab AK