Real-Time Optical Feedback for the Control of In Vivo Nanoparticle Concentration

描述（由申请人提供）：临床迫切需要加强对靶向药物递送和准确性的监测，癌症的发生和扩散，以及癌症治疗的纵向监测。纳米技术有望解决这个问题。一种能够选择性靶向的“智能”粒子将增强医生正确诊断所需的工具，并允许对治疗和后续过程进行实时监控。在理想的临床研究中，为了达到满意的治疗效果，每个受试者都应该注射与受试者体重和肿瘤负荷相关的精确数量的纳米颗粒。我们建议纳米光谱生物科学公司与路易斯安那理工大学生物医学工程系合作，测试一种廉价的、临床应用的光学工具的可行性，该工具可以提供即时的定量信息，以支持治疗相关纳米颗粒的输送和循环。Tech将独立开发一个临床原型，将其放置在手指或其他光学可及的位置，以监测输送剂量的准确性，并在静脉输送后立即评估有效循环时间，但在治疗干预之前。将评估该原型提供三个临床目标的可行性：(1)实时反馈，为从业者提供瞬时初始剂量验证；(2)实时反馈提供治疗剂量验证（np*min/mL），这是一种整合给药剂量和循环时间的药代动力学分析；(3)报警系统，识别非典型的缩短循环时间，可以帮助预测对纳米颗粒的生理反应，可能需要医疗干预。该项目的社会目标是“加速纳米技术的工作……将纳米技术与癌症应用相结合……通过能够绕过生物屏障的多功能靶向设备，在不损害健康组织的情况下，将高浓度的多种治疗药物直接输送到癌细胞和组织中，从而显著减少癌症的不良影响。”这笔赠款还旨在通过开发易于使用的具有成本意识的仪器来处理癌症健康差异问题，这些仪器专门设计用于解决“许多因素的影响，包括医生经验、医院环境和每个病人所在社区的社会人口统计”。

DESCRIPTION (provided by applicant): There is an immediate and urgent clinical need to enhance the monitoring of the delivery and accuracy of targeted drug delivery, the onset and spread of cancers, and the longitudinal monitoring of cancer treatments. Nanotechnology holds the promise to address this problem. A "smart" particle capable of selective targeting would augment the physician's tools needed for correct diagnosis and allow the treatment and follow-up procedures to be monitored in real-time. In an ideal clinical study, each subject would be injected with a precise number of nanoparticles related to the weight and tumor-burden of the subject in order to achieve a satisfactory therapeutic result. We propose that Nanospectra Biosciences, Inc. will join with the Biomedical Engineering Department at Louisiana Tech University (Ruston, LA) to test the feasibility of an inexpensive, clinically applicable optical tool to provide instantaneous quantitative information to support the delivery and circulation of therapeutically relevant nanoparticles. Independently, Tech will develop a clinical prototype, to be placed on a finger or other optically accessible location, in order to monitor the accuracy of the delivered dose and assess the effective circulation time immediately after intravenous delivery but prior to therapeutic intervention. The feasibility of the prototype to provide three clinical objectives will be assessed: (1) real- time feedback for practitioners to provide instantaneous initial dose verification, (2) real-time feedback providing therapeutic dose verification (np*min/mL), which is a pharmacokinetic analysis integrating the delivered dose and the circulation time, and (3) an alarm system which identifies a uncharacteristic shortened circulation time, which could help predict a physiological reaction to the nanoparticles, and which may require a medical intervention. This project's societal goals are to "accelerate work in nanotechnology, ...linking nanotechnology into cancer applications ... to dramatically reduce the adverse effects of cancer with multifunctional, targeted devices capable of bypassing biological barriers to deliver multiple therapeutic agents in high concentrations directly to cancer cells and tissues while sparing healthy tissue." This grant is also designed to deal with the problems of cancer health disparities, by developing easy-to-use cost-conscious instrumentation designed specifically to address the "impact of many factors, including physician experience, hospital environment, and the socio-demographics of each patient's neighborhood". PUBLIC HEALTH RELEVANCE: Nanoparticles hold significant promise for new and improved therapeutic and imaging applications and are being widely investigated. Preclinical and clinical use is affected by the "bio-availability" of these materials in vivo. This research proposal will develop a new device for real-time tracking of circulation kinetics for these new materials.