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

用于癌症成像和治疗的肿瘤靶向纳米粒子递送系统

• 批准号: 9899949
• 负责人: Tamara Minko
• 金额: $ 44.91万
• 依托单位: RUTGERS, THE STATE UNIV OF N.J.
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-04-21 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9899949
• 关键词: Antineoplastic Agents; Cancer Detection; Contrast Media; Detection; Development; Diagnostic; Disease; Disseminated Malignant Neoplasm; Drug Delivery Systems; Drug Kinetics; Early Diagnosis; Formulation; Future; GNRH1 gene; Goals; Gonadotropin-Releasing Hormone Receptor; Image; Image Enhancement; Inhalation; Intravenous; Investigation; Liposomes; Lung; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of lung; Malignant neoplasm of ovary; Medical Research; Modality; Neoplasm Metastasis; Paclitaxel; Patients; Pharmaceutical Preparations; Primary Neoplasm; Probability; Property; Public Health; Research; Route; Screening for cancer; Specificity; System; Therapeutic; Tissues; Treatment Side Effects; Water; base; cancer cell; cancer therapy; cancer type; chemotherapy; clinical practice; effective therapy; human model; imaging system; improved; in vitro testing; in vivo; in vivo evaluation; manganese oxide; mouse model; nanoparticle; nanoparticle drug; neoplastic cell; overexpression; particle; peptide hormone; pre-clinical; side effect; success; targeted cancer therapy; targeted treatment; theranostics; therapy outcome; tumor

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.

项目名称：用于癌症成像和治疗的肿瘤靶向纳米粒子递送系统 项目概要 癌症的早期发现大大增加了其成功和有效治疗的可能性。 治疗诊断学是医学研究中的一个新兴领域，有可能改善患者的整体治疗和 尽管纳米颗粒具有不同的特性，但它可以通过结合诊断和特定的治疗特性来获得结果。 在不同疾病的治疗领域具有优势，诊断与治疗相结合 单个纳米颗粒中的形态可能与某些困难相关，因此，它可能是理想的。 开发一种独立但集成的多粒子系统用于癌症检测的功效。 通过磁共振成像（MRI）和化疗可以确定原发肿瘤和转移灶 通过靶向含有造影剂或抗癌药物的纳米颗粒，显着改善 对于检查的癌细胞，计划研究的总体目标包括发展， 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 在目前的治疗诊断研究中，氧化锰。 纳米颗粒（Mn3O4）将用作MRI造影剂；水溶性较差的抗癌药物紫杉醇 (PTX) – 作为抗癌药物；中性脂质体 – 作为修饰的黄体生成激素的载体； 释放激素 (LHRH) 肽 - 作为靶向部分，开发的多颗粒治疗诊断系统将。 使用人类卵巢癌和肺癌的小鼠模型进行体外和体内测试。 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 与其他类型的癌症一样，该提案的具体目标是：（1）合成并表征癌症- (2) 评价合成的效果 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瘤 (3)评价剂型和给药途径的整体效果 紫杉醇的身体组织分布和药代动力学；（4）检查体内抗肿瘤功效和 聚乙二醇化癌症靶向脂质体联合成像和化疗的不良副作用 含有 PTX 的肺癌原位小鼠模型经静脉和吸入给药后。 预计所提出的方法和开发的基于癌症靶向纳米颗粒的 MRI 的使用 造影剂和化疗药物将大大提高原发性肿瘤的检测效果 肿瘤和转移以及癌症治疗，同时限制治疗的不良副作用。 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，并改善 肺癌和其他类型癌症的治疗效率。