GOLD NANOCAGES AS A NEW CLASS OF THERAPEUTIC AGENTS FOR PHOTOTHERMAL CANCER TREAT

描述（由申请人提供）：该合作项目涉及圣路易斯华盛顿大学生物医学工程系和放射学系的研究人员。这项工作的最终目标是开发和验证具有靶向配体的金纳米笼作为一类新型治疗剂，它可以作为纳米级换能器有效地将近红外光转化为热，并选择性地杀死癌细胞而没有任何不良副作用。本研究的范围包括：i)开发大规模生产具有可控尺寸、壁厚、吸收截面和表面功能的金纳米笼的可靠方法；ii)了解金纳米笼的体外靶向能力和在光热破坏癌细胞中的作用；iii)评估聚乙二醇化金纳米笼的生物分布，并在动物模型中最大化其被动靶向肿瘤的能力；iv)开发具有合适尺寸和表面化学性质的金纳米笼，用于在动物模型中结合被动和主动靶向肿瘤；v)在动物模型中验证和优化功能化金纳米笼用于肿瘤光热破坏的应用。如果成功，这项技术将为癌症治疗提供一种非常有效和选择性的方法。通过改变吸收与散射截面的比例，功能化的金纳米笼也可以作为分子造影剂用于许多成像方式，包括光学相干断层扫描（OCT）、光声断层扫描（PAT）、双光子荧光以及CT（因为金也是x射线的强吸收剂）。因此，金纳米笼有可能成为一种新型的双重药物，用于诊断和治疗

DESCRIPTION (provided by applicant): This collaborative program involves investigators from Departments of Biomedical Engineering and Radiology at Washington University in St. Louis. The ultimate goal of this work is to develop and validate Au nanocages with targeting ligands as a novel class of therapeutic agents, which can serve as nanoscale transducers to effectively convert NIR light into heat and selectively kill cancer cells without any adverse side effects. The scope of this research includes: i) developing robust methods for large-scale production of Au nanocages with controlled size, wall thickness, absorption cross section, and surface functionality; ii) understanding the in vitro targeting capability and the role of Au nanocages in photothermal destruction of cancer cells; iii) assessing the biodistribution of PEGylated Au nanocages and maximizing their capability for passive targeting of tumor in an animal model; iv) developing Au nanocages with the right size and surface chemistry for a combination of passive and active tumor targeting in an animal model; and v) validating and optimizing the use of functionalized Au nanocages for photothermal destruction of tumor in an animal model. If successful, the technology to be developed in this application will provide a highly effective and selective method for cancer treatment. By varying the ratio of absorption to scattering cross section, the functionalized Au nanocages could also serve as molecular contrast agents for a number of imaging modalities, including optical coherence tomography (OCT), photoacoustic tomography (PAT), two-photon fluorescence, as well as CT (because Au is also a strong absorber of X-ray). As a result, Au nanocages have the potential to become a novel class of dual agents for both diagnostic and therapeutic applications PUBLIC HEALTH RELEVANCE: The ultimate goal of this work is to develop and validate gold nanocages with targeting ligands as a novel class of therapeutic agents, which can serve as nanoscale transducers to effectively convert NIR light into heat and selectively kill cancer cells without any adverse side effects. If successful, the technology to be developed in this application will provide a highly effective and selective method for cancer treatment. By varying the ratio of absorption to scattering cross section, the gold nanocages could also serve as molecular contrast agents for a number of imaging modalities, including optical coherence tomography, photoacoustic tomography, two-photon fluorescence, as well as computed tomography (because gold is also a strong absorber of X-ray). To this end, gold nanocages have the potential to become a novel class of dual agents for both diagnostic and therapeutic applications.