Theranostic nanoparticles for the treatment of RAI refractory thyroid cancer

描述(由申请人提供)：在尽量减少不必要的分布的同时，特定部位的药物输送一直是癌症治疗中追求的目标之一。在这项工作中，我们开发了基于聚合物的药物传递载体，其在体内的分布也可以通过磁共振成像进行定量成像，从而实现全身、实时绘制药物分布的地图，并测量药代动力学、药效学和毒性曲线。该方案的两个创新方面是1)具有极高稳定性、大滞留率的聚合物药物载体 药物的容量，以及与不同抗癌药物和靶向配体组装的多功能性；2)用于体内顺磁造影剂定量测量的新MRI技术。这些方面满足了对药物递送载体的要求，即“无痛的”。基于我们最近发现一种称为细胞间黏附分子-1的分子与甲状腺癌的恶性程度高度相关，我们建议开发紫杉醇药物载体作为甲状腺癌的一种新的治疗方式。这项提议将实现的两个具体目标是：1)开发生产和验证治疗纳米颗粒的综合方案，并用于体外药物疗效和成像技术的评估；2)确定药物载体的时空分布，以及治疗效果和毒性曲线，以定量评估肿瘤与药物的相互作用。总体而言，我们的药物载体的治疗能力将在小鼠体内人甲状腺癌的异位和原位移植中得到证明，这项研究旨在验证开发的药物载体未来用于治疗侵袭性、转移性和放射性碘难治性甲状腺癌。

DESCRIPTION (provided by applicant): Site-specific delivery of drugs while minimizing unwanted distribution has been one of the pursued goals in cancer therapy. In this endeavor, we have developed polymer-based drug delivery carriers, whose distribution in vivo can also be quantitatively imaged by MRI, enabling whole body, real-time mapping of drug distribution, and measurements of pharmacokinetic, pharmacodynamic, and toxicity profiles. Two innovative aspects in this proposal are 1) polymeric drug carriers with exceptional stability, large retention capacity of drugs, and versatility in assembly with diverse cancer drugs and targeting ligands and 2) novel MRI techniques for quantitative measurement of paramagnetic contrast agents in the body. These aspects fulfill the requirement for drug delivery carriers to be 'theranostic'. Motivated by our recent findings that a molecule called the intercellular adhesion molecule (ICAM)-1 is highly expressed in correlation with the malignancy of thyroid cancer, we propose to develop the theranostic drug carriers loaded with Paclitaxel as a new treatment modality of thyroid cancer. Two specific aims that will be achieved in this proposal are: 1) Develop comprehensive protocols for production and validation of theranostic nanoparticles, and for in vitro evaluation of drug efficacy and imaging techniques; 2) Determine spatiotemporal distribution of drug carriers, and therapeutic efficacy and toxicity profiles to quantitatively assss tumor-drug interactions. Overall, theranostic capability of our drug carriers will be demonstrated in ectopic and orthotopic xenografts of human thyroid carcinomas in mice, a study designed to validate developed drug carriers for future use to treat aggressive, metastatic, and radioactive iodine refractory thyroid cancer.