Minimally-Invasive Image-Guided Therapy for Cancer Treatment

描述(申请人提供)：这项研究的长期目标是开发一种技术，并最终开发一种用于癌症的图像引导光动力疗法的微创商业系统。这当然与NCI对癌症筛查、诊断、进展、影像指导治疗、治疗监测和复发的体内成像的关注是一致的。在犹他大学药剂学系进行的研究中，卢教授的研究团队设计并合成了一种包含磁共振造影剂和光敏剂的双功能聚合物，并在双功能结合物的MRI中展示了对小鼠肿瘤的强烈可视化，以及对肿瘤进行光动力学治疗时的良好治疗效果。ContraDyn公司已经获得了允许这一进步的技术许可。因此，这项建议是犹他大学、发明家和ContraDyn，Inc.共同努力的结果。在卢教授工作的基础上，这项建议将纳入一种特定的靶向试剂，以减少人们接触的化学物质的数量。光动力疗法仍然面临的挑战包括向靶组织输送足够的光敏剂，以及靶组织的准确光照射。该计划的最终目标是为光敏剂和成像探针提供高效的靶向药物输送系统。具体地说，这笔赠款将使我们能够1)设计、合成和表征肿瘤特异性的双功能聚合物；2)在肿瘤-小鼠模型中评估几种剂量的靶向双功能聚合物用于肿瘤成像和癌症治疗的有效性；3)优化合成和分析方法，以获得最安全的靶向双功能聚合物配方。与公共卫生相关：光动力疗法已被证明是治疗无法进行手术或对化疗耐药的癌症的有效方法。目前，光动力疗法很难在不损害周围正常组织的情况下移除、消融或治疗肿瘤组织。添加肿瘤靶向剂和改进的递送系统应该会产生更好的结果，并减少对周围组织的损害。

DESCRIPTION (provided by applicant): The long-term objective of this research is to develop a technology and eventually a minimally-invasive commercial system for image-guided photodynamic therapy for cancer. This is certainly in keeping with NCI's focus on imaging in vivo for cancer screening, diagnosis, progression, image-guide therapy, treatment monitoring, and recurrence. In studies conducted at the University of Utah's Department of Pharmaceutics, Professor Lu's research team has designed and synthesized a bifunctional polymer containing an MRI contrast agent and a photosensitizer, and has demonstrated strong visualization of mouse tumors in MRI with the bifunctional conjugate, and good therapeutic efficacy when tumors were treated photodynamic therapy. ContraDyn, Inc. has licensed the technology which has allowed for this advance. Thus this proposal is a collaborative effort among the University of Utah, the inventor, and ContraDyn, Inc. Building on Professor Lu's work this proposal will incorporate a specific targeting agent to reduce the amount of chemicals to which people would be exposed. Challenges still to be met for photodynamic therapy include delivery of sufficient photosensitizer to target tissues, and accurate light-irradiation of the target. An efficient targeted drug-delivery system for both the photosensitizer and imaging probe is the ultimate goal of this program. Specifically, this grant would allow us to 1) design, synthesize, and characterize a tumor-specific targeted, bifunctional polymer; 2) evaluate the efficacy of the targeted, bifunctional polymer for tumor imaging and cancer treatment in a tumor-mouse model at several doses; and 3) optimize the synthesis and analytical methods for the safest formulation of the targeted, bifunctional polymer. PUBLIC HEALTH RELEVANCE: Photodynamic therapy has been shown to be an effective approach for treating cancers which are not accessible to surgery or are resistant to chemotherapy. Currently with photodynamic therapy it is difficult to remove, ablate, or treat tumor-tissue without harming the surrounding normal tissue. Addition of tumor-targeting agents and improved delivery systems should result in better outcomes and reduced damage to surrounding tissues.