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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要/摘要手术后残留的癌细胞会增加癌症复发的机会几乎在所有癌症亚型中。目前无法在手术期间识别这些肿瘤细胞阻碍了各种癌症治疗，包括乳腺癌和前列腺癌，20-40% 这些患者的切缘呈阳性，这使得癌症复发的风险加倍。该提案通过超灵敏光学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由于固有的原因，无法在组织表面和深度上实现高灵敏度当前光学探头及其必需的成像器的物理限制。它们也太笨重了集成到现代手术工具中，可以更有效地指导精准手术精度比今天可以达到的更高。在这里，我们通过引入一个完整的解决方案来解决这些双重挑战整合纳米技术、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术中成像表面和深度。我们提出纳米技术的重大进展来重新设计上转换纳米粒子作为光学探针，可以在组织、蛋白质中安全成像工程生产选择性地将探针靶向肿瘤的抗体和检测器工程构建超薄成像芯片，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仪显着提高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。