Chip-Scale Intraoperative Optical Navigation with Immunotargeted Upconverting Nanoparticles

项目总结/摘要 手术后残留的癌细胞增加了癌症复发的机会 几乎所有的癌症亚型。目前无法在手术中识别这些肿瘤细胞 阻碍了包括乳腺癌和前列腺癌在内的各种癌症的治疗，因为20-40%的 这些患者的边缘呈阳性，这使癌症复发的风险增加了一倍。 该建议通过用于超灵敏光学成像的原始方法解决了这个问题。 活组织中和手术期间的癌细胞成像。目前的术中成像方法 不能在组织表面和深度上实现高灵敏度 当前光学探针和它们所需的成像器两者的物理限制。它们也太笨重了 集成到现代手术工具中，可以更大程度地指导精确手术 比现在更准确。在这里，我们通过引入一个全面的 整合纳米技术、蛋白质工程和先进成像仪的新成像策略 设计的目标是对癌细胞进行实时高灵敏度的术中成像， 表面和深度。我们提出纳米技术的重大进展， 上转换纳米颗粒作为光学探针，可以在组织、蛋白质 工程化以产生选择性地将探针靶向肿瘤的抗体，以及检测器 工程师们建造了一个可直接集成到手术器械中的MRI成像芯片。 这些新技术的结合将仪器本身转变为成像器， 大大提高了识别癌细胞的灵敏度，最终目标是能够 以真实的时间来识别所有残留的疾病。

Project Summary/Abstract Residual cancer cells left behind following surgery increase the chance of cancer returning in almost every cancer subtype. The current inability to identify these tumor cells during surgery hinders cancer care across the spectrum, including breast and prostate cancers, as 20-40% of these patients suffer from positive margins, which doubles the risk of cancer returning. This proposal solves this problem through an original approach for ultrasensitive optical imaging of cancer cells in live tissue and during surgery. Current intraoperative imaging methods are unable to achieve high sensitivity both on the tissue surface and at depth due to inherent physical limits of both current optical probes and their requisite imagers. They are also too bulky to be integrated onto modern surgical tools, which could guide precision surgery with far greater accuracy than achievable today. Here, we address these dual challenges by introducing a wholly new imaging strategy integrating nanotechnology, protein engineering, and advanced imager design with the goal of real-time highly sensitive intraoperative imaging of cancer cells, both on the surface and at depth. We propose major advances in nanotechnology to redesign upconverting nanoparticles as optical probes that can be safely imaged in tissue, protein engineering to produce antibodies that selectively target the probes to tumor, and detector engineering to build an ultrathin imaging chip, directly integrated into surgical instrumentation. The combination of these novel technologies transforms instruments themselves into imagers to dramatically increase the sensitivity in identifying cancer cells, with the ultimate goal of being able to identify, in real time, all residual disease.