NANOPHOTOSENSITIZERS FOR REGENERATIVE PHOTOTHERAPY OF TUMORS

用于肿瘤再生光疗的纳米光敏剂

基本信息

批准号：
10164004
负责人：
Samuel Achilefu
金额：
$ 45.07万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-08-01 至 2021-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10164004
关键词：
A549 Address Animal Cancer Model Animal Model Antioxidants Biodistribution Biological Carbon Cell model Cells Cherenkov Radiation Clinical Dependence Disease Endoscopes Engineering Enzymes Excretory function Exhibits Free Radicals Glucose Harvest Hydroxyl Radical Hypoxia Image In Transferrin Intervention Kidney Label Lesion Light Lipids Liver Magnetic Resonance Imaging Magnetism Mediating Medicine Methods Molecular Nucleic Acids Organ Organelles Oxidation-Reduction Oxygen PUVA Photochemotherapy Pathologic Penetration Pharmaceutical Preparations Photosensitization Photosensitizing Agents Phototherapy Positron Positron-Emission Tomography Precision therapeutics Process Prodrugs Proliferating Property Proteins Quantum Dots Radiation Radioisotopes Radiolabeled Reactive Oxygen Species Science Singlet Oxygen Site Solid Neoplasm Source Surface TFRC gene Technology Therapeutic Therapeutic Effect Tissues Toxic effect Transducers Transferrin Treatment Efficacy Ultraviolet Rays absorption alternative treatment analog cancer cell cancer therapy cell type cellular imaging cytotoxic cytotoxicity effective therapy free radical oxygen human disease imaging agent improved in vivo light dosimetry nano nanomaterials nanoparticle nanoscale neoplastic cell optical imaging overexpression photoactivation receptor regenerative spatiotemporal therapy outcome titanium dioxide treatment optimization tumor uptake

项目摘要

Abstract 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 and/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, but 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 can be achieved by harnessing the ability of some INPs to serve as efficient nanoscale energy transducers. Quantum dots, upconversion NPs, carbon nanomaterials, and photocatalytic NPs such as titanium dioxide nanoparticles 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 photosentizers, which confines therapy to shallow lesions, and the frequent reliance on oxygen to generate cytotoxic reactive oxygen species, which precludes effective treatment under the hypoxic conditions found in many solid tumors. We hypothesize that photoactivation of low radiance-sensitive nanophotosensitizers via depth-independent Cerenkov radiation will generate cytotoxic free radicals in an oxygen- independent manner for effective therapy. In this proposal, we will (1) Synthesize and optimize tumor-targeting nanophotosensitizers for effective spatiotemporal therapy of diseases; and (2) optimize orthogonally targeted radionuclides for selective delivery of Cerenkov radiation to pathologic cells and tissue. Using animal models of cancer, we will determine the efficacy of Cerenkov radiation mediated nano-phototherapy.

抽象的无机纳米颗粒（INP）具有独特的特性，有利于其多样化的应用医学，工程，科学和技术。这些的较大的地表与体积比 INP提供用于附着多种药物和/或成像剂的地点，以进行治疗和各种人类疾病的成像。生物实体（例如蛋白质）的进一步共轭核酸和脂质赋予这些INP的特定靶向体内所需的组织。最近的研究表明，可以利用某些INP的固有特性进行治疗结果，但是通过相互作用的固有治疗作用自发刺激具有细胞内细胞器，蛋白质或分子过程的NP很难控制，导致明显的目标毒性。可以通过利用来实现另一种治疗方法某些INP充当有效的纳米级能传感器的能力。量子点，上转化的NP，碳纳米材料和光催化NP，例如二氧化钛纳米颗粒是一些在治疗中显示出希望的纳米级能传感器人类疾病。这些纳米光增敏剂的出色氧化还原特性可提供较高的吸收光后，时空控制和精确光疗。两个主要限制当前的光质干预措施是用于激活的光的有限渗透摄影剂，将治疗局限于浅病变，并且频繁依赖氧气为了产生细胞毒性活性氧，这排除了在在许多实体瘤中发现的低氧条件。我们假设通过独立于深度的Cerenkov辐射将在氧气中产生细胞毒性自由基有效治疗的独立方式。在此提案中，我们将（1）合成和优化针对性疾病时空治疗的肿瘤纳米增敏剂；（2）优化正交靶向放射性核素，以选择性地递送Cerenkov辐射到病理细胞和组织。使用癌症的动物模型，我们将确定 Cerenkov辐射介导的纳米疗法。

项目成果

期刊论文数量（16）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Utilizing the Multiradionuclide Resolving Power of SPECT and Dual Radiolabeled Single Molecules to Assess Treatment Response of Tumors.

DOI：
10.1007/s11307-015-0842-8
发表时间：
2015-10
期刊：
Molecular imaging and biology
影响因子：
3.1
作者：
Xu B;Shokeen M;Sudlow GP;Harpstrite SE;Liang K;Cheney PP;Edwards WB;Sharma V;Laforest R;Akers WJ;Achilefu S
通讯作者：
Achilefu S

Breaking the depth dependency of phototherapy with Cerenkov radiation and low-radiance-responsive nanophotosensitizers.

DOI：
10.1038/nnano.2015.17
发表时间：
2015-04
期刊：
Nature nanotechnology
影响因子：
38.3
作者：
通讯作者：

Monodispersed calcium carbonate nanoparticles modulate local pH and inhibit tumor growth in vivo.

DOI：
10.1039/c5nr06162h
发表时间：
2016-07-07
期刊：
Nanoscale
影响因子：
6.7
作者：
Som A;Raliya R;Tian L;Akers W;Ippolito JE;Singamaneni S;Biswas P;Achilefu S
通讯作者：
Achilefu S

Inactivation of multidrug-resistant bacteria and bacterial spores and generation of high-potency bacterial vaccines using ultrashort pulsed lasers.

DOI：
10.1002/jbio.202100207
发表时间：
2022-03
期刊：
Journal of biophotonics
影响因子：
2.8
作者：
Tsen SD;Popovich J;Hodges M;Haydel SE;Tsen KT;Sudlow G;Mueller EA;Levin PA;Achilefu S
通讯作者：
Achilefu S

Probing distance-dependent plasmon-enhanced near-infrared fluorescence using polyelectrolyte multilayers as dielectric spacers.