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

项目名称：肿瘤靶向纳米微粒给药系统用于肿瘤的成像和治疗 项目摘要 癌症的早期发现大大增加了其成功和有效治疗的可能性。 体视学是医学研究中的一个新兴领域，它可能会改善整体患者的治疗和 通过结合诊断和特定的治疗特性来判断结果。尽管纳米颗粒允许不同的 在不同疾病的治疗领域具有优势，诊断和治疗相结合 单个纳米颗粒中的模式可能与某些困难相关。因此，理想的做法可能是 开发一种分离的、但集成的多粒子系统用于治疗。癌症检测的功效 通过磁共振成像(MRI)和化疗可以发现原发肿瘤和转移瘤 通过靶向含有造影剂或抗癌药物的纳米颗粒显著改善 对癌细胞来说。因此，计划调查的总体目标包括发展， 磁共振多粒子肿瘤靶向诊断系统的表征及临床前体内试验 以及原发肿瘤和转移瘤的化疗。在目前的治疗研究中，氧化锰 纳米粒(Mn3O4)将用作磁共振造影剂；难于溶于水的抗癌药物紫杉醇 (PTX)-作为抗癌药物；中性脂质体-作为PTX的载体；一种改良的黄体生成素 释放激素(LHRH)多肽-AS靶向部分。开发的多粒子热疗系统将 在体外和体内使用人类卵巢癌和肺癌的小鼠模型进行测试。然而，拟议的 该方法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)合成和表征癌症- 靶向纳米粒子用于肿瘤的成像和治疗；(2)评价合成的 纳米粒子作为磁共振造影剂在小鼠体内检测原发肿瘤和转移瘤 建立肺癌和卵巢癌模型；(3)评价制剂和给药途径对整体的影响。 紫杉醇的体内组织分布和药代动力学及(4)体内抗肿瘤作用和药代动力学 聚乙二醇化肿瘤靶向脂质体联合化疗的不良反应 用含PTX的小鼠原位肺癌模型静脉和吸入给药。它是 期望提出的方法和所开发的癌症靶向纳米颗粒磁共振成像的使用 造影剂和化疗药物将大幅提高对原发性肺癌的检测效果 肿瘤和转移以及癌症治疗，同时限制治疗的不良副作用。这个 计划中的研究有可能显著影响成像和药物输送领域，并改善 肺癌和其他类型癌症的治疗效率。

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.