Chip-Scale Intraoperative Optical Navigation with Immunotargeted Upconverting Nanoparticles

使用免疫靶向上转换纳米颗粒的芯片级术中光学导航

• 批准号: 10743477
• 负责人: Mekhail Anwar
• 金额: $ 65.53万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-15 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10743477
• 关键词: Address; Affinity; Alloys; Animal Model; Antibodies; Antibody Specificity; Binding; Biological Assay; Breast Cancer Model; Cancer Detection; Cell Culture Techniques; Clinical; Coupled; Deposition; Detection; Development; Diffuse; Disease; Engineering; Excision; G-substrate; Goals; Image; Image-Guided Surgery; Imaging technology; Immunoglobulin G; Individual; Label; Lanthanoid Series Elements; Lasers; Left; Lymph Node Involvement; Malignant Neoplasms; Malignant neoplasm of prostate; Microscope; Microscopic; Modeling; Modernization; Mus; Nanotechnology; Nature; Operative Surgical Procedures; Optics; Outcome; Patients; Photons; Protein Engineering; Proteins; Recombinants; Resectable; Residual Cancers; Residual Neoplasm; Sensitivity and Specificity; Silicon; Speed; Surface; Surgical Instruments; Surgical Models; Surgical margins; Technology; Testing; Thinness; Time; Tissue Sample; Tissue Stains; Tissue imaging; Tissues; Toxic effect; Visible Radiation; Visualization; Xenograft Model; absorption; antibody engineering; biomaterial compatibility; cancer care; cancer cell; cancer imaging; cancer risk; cancer subtypes; cancer surgery; crosslink; design; detector; diagnostic platform; fluorophore; imager; imaging modality; improved; improved outcome; instrument; instrumentation; integrated circuit; light emission; lymph nodes; malignant breast neoplasm; meter; microscopic imaging; molecular imaging; nano; nanocrystal; nanoparticle; nanoshell; neoplastic cell; new technology; novel; optical imaging; pre-clinical; sensor; theranostics; tool; tumor; two-photon

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.

项目摘要/摘要 手术后残留癌细胞增加癌症复发几率 几乎在每一种癌症亚型中。目前在手术中无法识别这些肿瘤细胞 阻碍包括乳腺癌和前列腺癌在内的所有癌症的护理，因为20%-40%的人 这些患者的利润率为正，这会使癌症复发的风险增加一倍。 该方案通过一种新颖的超灵敏光学方法解决了这个问题 对活组织和手术中的癌细胞进行成像。目前的术中影像检查方法 由于固有的原因，无法在组织表面和深度上实现高敏感性 目前的光学探头及其所需成像器的物理限制。它们也太笨重了 集成到现代手术工具上，可以更好地指导精确手术 精确度比今天所能达到的要高。在这里，我们通过引入一个完整的 集成纳米技术、蛋白质工程和先进成像仪的新成像策略 设计的目标是在术中对癌细胞进行实时高灵敏度成像，这两种方法都是 表面和深度。我们建议在纳米技术方面取得重大进展，以重新设计 将纳米颗粒上转换为光学探针，可以安全地在组织、蛋白质中成像 制造选择性靶向肿瘤探针的抗体的工程，以及检测器 设计制造一种超薄成像芯片，直接集成到手术器械中。 这些新技术的结合将仪器本身转变为成像器，以 极大地提高了识别癌细胞的灵敏度，最终目标是能够 实时识别所有残留疾病。