Tumor-targeted nanoparticle-based delivery system for imaging and treatment of cancer

项目名称：用于癌症成像和治疗的基于肿瘤靶向纳米颗粒的递送系统 项目摘要 癌症的早期发现大大增加了成功和有效治疗的可能性。 治疗诊断学是医学研究中的一个新兴领域，可以潜在地改善整体患者治疗， 通过结合诊断和特定的治疗特性。虽然纳米颗粒允许不同的 在不同疾病的治疗领域的优势，诊断和治疗的组合 单个纳米颗粒中的形态可能与某些困难有关。因此，理想的是， 为治疗诊断学开发一个分离但集成的多粒子系统。癌症检测的功效 通过磁共振成像（MRI）和化疗的原发性肿瘤和转移， 通过靶向含有造影剂或抗癌药物的纳米颗粒， 到癌细胞。因此，计划调查的总体目标包括： 用于MRI诊断的多粒子癌症靶向系统的表征和临床前体内测试 以及原发肿瘤和转移瘤的化疗。在目前的治疗诊断学研究中，氧化锰 纳米颗粒（Mn 3 O 4）将用作MRI造影剂;水溶性差的抗癌药物紫杉醇 (PTX)- 作为抗癌药物;中性脂质体-作为PTX的载体;修饰的促黄体激素 释放激素（LHRH）肽-作为靶向部分。开发的多粒子治疗诊断系统将 使用人卵巢癌和肺癌的鼠模型在体外和体内进行测试。然而，拟议的 该方法也可以扩展到其他类型的载体/颗粒、造影剂和抗癌药物 和其他类型的癌症一样。该提案的具体目标是：（1）综合和描述癌症- 用于成像和治疗癌症的靶向纳米颗粒;（2）评估合成的 纳米颗粒作为MRI造影剂用于使用小鼠体内检测原发性肿瘤和转移 （3）评价制剂和给药途径对肺癌和卵巢癌的整体影响 紫杉醇的身体组织处置和药代动力学和（4）检查体内抗肿瘤功效和 聚乙二醇化肿瘤靶向脂质体联合成像和化疗的不良副作用 在静脉内和吸入递送后，使用原位小鼠肺癌模型观察含有PTX的紫杉醇对肺癌的治疗效果。是 我预计，提出的方法和使用开发的癌症靶向纳米粒子为基础的MRI 造影剂和化疗药物将显著增强原发性肿瘤检测的功效 肿瘤和转移以及癌症的治疗，同时限制治疗的不良副作用。的 计划中的研究有可能对成像和药物输送领域产生重大影响， 治疗肺癌和其他类型癌症的效率。

Project Title: Tumor-targeted nanoparticle-based delivery system for imaging and treatment of cancer Project Summary Early detection of cancer substantially increases the probability of its successful and effective treatment. Theranostics is an emerging field in medical research that can potentially improve overall patient therapy and outcome by combining diagnostic and specific therapeutic properties. Although nanoparticles allow for distinct advantages in the field of therapy of different diseases, a combination of both diagnostic and therapeutic modalities in a single nanoparticle may be associated with certain difficulties. Therefore, it may be ideal to develop a separated, but integrated multi-particle system for theranostics. The efficacy of the cancer detection by magnetic resonance imaging (MRI) and chemotherapy of primary tumors and metastases can be significantly improved by targeting of nanoparticles containing a contrast agent or anticancer drug specifically to cancer cells. Consequently, the overall goal of the planned investigations consists of the development, characterization, and preclinical in vivo testing of multi-particle cancer-targeted system for diagnostics by MRI and chemotherapy of primary tumors and metastases. In the present theranostic study, manganese oxide nanoparticles (Mn3O4) will be used as MRI contrast agents; poor water-soluble anticancer drug paclitaxel (PTX) – as an anticancer drug; neutral liposomes – as carriers for PTX; a modified luteinizing hormone releasing hormone (LHRH) peptide – as targeting moiety. The developed multi-particle theranostic system will be tested in vitro and in vivo using murine models of human ovarian and lung cancers. However, the proposed approach may be extended for other types of carriers/particles, contrast agents, and anticancer drugs as well as other types of cancer. The specific aims of the proposal are: (1) To synthesize and characterize cancer- targeted nanoparticles for imaging and treatment of cancers; (2) To evaluate the efficacy of the synthesized nanoparticles as MRI contrast agents for the detection of primary tumors and metastases in vivo using murine models of lung and ovarian cancers; (3) To evaluate the effect of formulation and drug delivery route on whole body tissue disposition and pharmacokinetics of paclitaxel and (4) To examine in vivo antitumor efficacy and adverse side effects of combined imaging and chemotherapy with PEGylated cancer-targeted liposomes containing PTX using orthotopic murine model of lung cancer after intravenous and inhalation delivery. It is expected that proposed approach and the use of the developed cancer-targeted nanoparticle-based MRI contrast agents and chemotherapeutic drug will substantially enhance the efficacy of the detection of primary tumors and metastases and therapy for cancers, while limiting adverse side effects of the treatments. The planned studies have the potential to significantly impact the field of imaging and drug delivery and to improve the efficiency of therapy of lung and other types of cancer.