NIR-Emissive Polymersomal Markers for Molecula-Level Detection of Metastasis

描述（由申请人提供）：早期癌或休眠或潜伏转移性肿瘤细胞的检测仍然是一个难以捉摸但重要的临床目标。我们寻求进一步开发革命性的新纳米技术，使转移性癌细胞的光学检测。为了实现这一目标，我们将进一步完善近红外（NIR）发射聚合物囊泡的设计标准，这是一种有前途的新的软物质纳米级平台，用于体内诊断和药物输送应用。该计划将开发（i）针对纳米级（ii）具有优化的发射输出的纳米级NIR发射聚合物囊泡，（iii）原型靶向纳米级囊泡，其中聚合物结构单元基于FDA批准的材料，（iv）具有理想细胞表面粘附动力学的靶向NIR发射聚合物囊泡，和（v）不仅提供对转移性疾病的新认识，而且定义用于体内休眠肿瘤细胞检测、诊断和治疗的可进化的纳米级平台的方法和技术。这些努力涉及将NIR荧光团结构和生物物理学、聚合物囊泡物质组成、囊泡机械和生物学性质、纳米级NIR发射聚合物囊泡荧光输出以及细胞靶向基序的性质与体内功能和功效相关联。因此，我们追求的实验方法是交叉和综合的，包括超分子化学合成，生物物理表征，体内成像，生物工程，生物学和医学。我们将努力建立设计原则，最终实现在临床相关诊断条件下实时检测和识别有限的靶细胞数量，并为转移性疾病的研究定义新的工具。

DESCRIPTION (provided by applicant): The detection of early carcinoma or dormant or latent metastatic tumor cells remains an elusive but important clinical goal. We seek to develop further revolutionary new nanotechnology that enables optically based detection of metastatic cancer cells. Towards this goal, we will further refine design criteria for near infrared (NIR) emissive polymersomes, a promising new soft matter nanoscale platform for in vivo diagnostic and drug-delivery applications. This program will develop (i) targeted nanoscale (diameter < 100 nm) NIR- emissive polymersomes, (ii) nanoscale NIR-emissive polymersomes having optimized emissive output, (iii) prototype targeted nanoscale vesicles in which the polymeric building blocks are based-upon FDA-approved materials, (iv) targeted NIR-emissive polymersomes with ideal cell-surface adhesion dynamics, and (v) methods and technology that provide not only new insights into metastatic disease, but define an evolvable nanoscale platform for in vivo dormant tumor cell detection, diagnosis, and treatment. These efforts involve correlating NIR fluorophore structure and photophysics, polymersome composition of matter, vesicle mechanical and biological properties, nanoscale NIR-emissive polymersome fluorescence output, and the nature of the cellular targeting motif, with in vivo function and efficacy. As such, the experimental approach we pursue is cross-cutting and integrative, encompassing supramolecular chemical synthesis, photophysical characterization, in vivo imaging, bioengineering, biology, and medicine. We will strive to establish design principles that will ultimately enable real-time detection and identification of limited target cell numbers under clinically relevant diagnostic conditions, and define new tools for the study of metastatic disease.