Biomolecule-Directed Assembly for Enhancing Near IR Energy Transfer Processes in Theranostics

用于增强治疗诊断学中近红外能量转移过程的生物分子定向组装

• 批准号: 9090086
• 负责人: Jennifer N Cha
• 金额: $ 17.21万
• 依托单位: UNIVERSITY OF COLORADO
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-01 至 2018-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9090086
• 关键词: 4T1; Adverse effects; Area; Biological Assay; Blood Circulation; Cells; Clinic; Complex; Deposition; Drug Delivery Systems; Dyes; Electron Microscopy; Energy Transfer; Energy-Generating Resources; Ensure; Environment; Evaluation; Future; Generations; Goals; Gold; Harvest; Health; Heating; Heterogeneity; Hybrids; Image; Knowledge; Label; Lead; Light; Luminescent Measurements; Malignant Neoplasms; Measurement; Measures; Methods; Morphology; Nanostructures; Output; Patients; Pharmaceutical Preparations; Phase Transition; Physiologic pulse; Polymers; Positioning Attribute; Process; Production; Reaction; Research; Singlet Oxygen; Site; Skin; Solid Neoplasm; Source; Stimulus; Structure; Sulfones; Surface; System; Techniques; Technology; Temperature; Testing; Theoretical Studies; Therapeutic; Tissues; Translations; Treatment Efficacy; Validation; Visible Radiation; absorption; anticancer research; cancer imaging; cancer therapy; cancer type; contrast imaging; depolymerization; design; in vitro Model; irradiation; luminescence; macromolecule; matrigel; nanoparticle; nanorod; nanoscale; particle; poly-N-isopropylacrylamide; response; theranostics; tumor; tumor heterogeneity

 DESCRIPTION (provided by applicant): The goal of the proposed research is to control the assembly and fabrication of discrete clusters of anisotropic gold nanostructures, UCNPs, and responsive polymer coatings to obtain ideal theranostics for the imaging and treatment of solid tumors. Theranostics represent an exciting area of cancer research because they allow noninvasive tracking of therapeutics into the tumor environment followed by tumor-specific release. Light in the "tissue transparency window" of 650-1000 nm can serve as an energy source to perform both of these functions. However, most IR-induced imaging and therapy requires light flux only available at superficial sites and thus cannot be applied to many other cancers. The proposed research will utilize the PIs' knowledge of photophysics, nanoscale assembly, and macromolecules for the rational design of NIR-utilizing nanostructures. The proposed theranostic will produce either visible image contrast or drug release, depending on irradiation intensity. The proposed nanostructures will consist of an anisotropic gold nanostructure for NIR maximum absorption, an upconverting nanoparticle (UCNP) for conversion to visible light, and a stimulus-responsive polymer coating to release drug molecules in response to irradiation. A nanostructure able to perform these functions at non-superficial depths requires both a fundamental understanding of the energy transfer processes occurring at the gold surface and the mechanisms by which this energy can be harvested. This will be accomplished through: 1. Synthesis of precise Au-UCNP nanostructures and characterization of photoluminescence. Recent theoretical studies have shown that local field enhancement can enhance upconverted luminescence output by orders of magnitude if the particles are assembled correctly. Biomolecular assembly techniques will be used to specifically position UCNPs at the tips of anisotropic Au nanorods (AuNRs) and nanostars (AuNSs) to maximize energy transfer. These structures will be validated using both single particle and ensemble luminescence measurements. 2. Synthesis of thermally-responsive and photodegradable polymers and evaluation of their responsiveness to NIR irradiation of Au-UCNP clusters. The deposition of IR energy at the surface of the Au nanostructures will be employed to facilitate drug delivery by surface-grafted polymers via either Au surface heating or generation of singlet oxygen. These studies will be performed using polymers capable of conformational switching or oxidative depolymerization, respectively. 3. Synthesis of optimized Au-UCNP-polymer theranostics and validation in in vitro models. The imaging and therapeutic capabilities of the optimized theranostics will be tested against 4T1 cells grown in a 3D Matrigel substrate to mimic both the structure and heterogeneity of the tumor environment.

 描述（由应用程序提供）：拟议的研究的目的是控制各向异性金纳米结构，UCNP和响应式聚合物涂层的离散簇的组装和结构，以获得理想的疗法，以进行固体瘤的成像和处理。治疗学代表了癌症研究的一个令人兴奋的领域，因为它们允许将治疗剂进行非侵入性跟踪到肿瘤环境中，然后进行肿瘤特异性释放。 650-1000 nm的“组织透明窗口”中的光作为执行这两种功能的能源。但是，大多数IR诱导的成像和治疗都需要仅在表面部位可用的光通量，因此不能应用于许多其他癌症。拟议的研究将利用PIS的摄影知识，纳米级装配和大分子的知识来实现​​NIR利用纳米结构的合理设计。拟议的热静态性将产生可见的图像对比度或药物释放，具体取决于辐射强度。所提出的纳米结构将包括各向异性金纳米结构，用于NIR最大吸收，向上转化的纳米颗粒（UCNP）以转化为可见光，以及刺激响应的聚合物涂层以释放出对受发射的响应的药物分子。纳米结构可以在非表面深度执行这些功能，这既需要对在金表面发生的能量传递过程的基本了解，又需要收集该能量的机制。这将通过：1。精确的Au-UCNP纳米结构的合成和光燃料的表征。最近的理论研究表明，如果正确组装粒子，则局部场的增强可以通过数量级来增强向上的发光输出。生物分子组装技术将用于特异性定位UCNP，在各向异性AU纳米棒（Aunrs）和纳米级（AUNSS）的尖端上，以最大程度地提高能量传递。这些结构将使用单个粒子和集合发光测量值验证。 2。热响应和光降解聚合物的合成以及对Au-UCNP簇的NIR照射的响应能力的评估。将雇用IR能量在AU纳米结构表面的沉积，以通过AU表面加热或单粒氧的产生来促进表面接枝聚合物的药物递送。这些研究将分别使用能够构象开关或氧化物解聚的聚合物进行。 3。在体外模型中的优化Au-UCNP聚合物疗法和验证的合成。优化热词的成像和治疗能力将针对在3D矩阵底物中生长的4T1细胞进行测试，以模仿肿瘤环境的结构和异质性。