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: 10115624
• 负责人: Tamara Minko
• 金额: $ 44.17万
• 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 2024-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10115624
• 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; diagnostic platform; effective therapy; efficacy evaluation; 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：基于肿瘤的纳米颗粒输送系统，用于成像和治疗癌症 项目摘要 癌症的早期发现大大增加了其成功有效治疗的可能性。 疗法是医学研究的新兴领域，可以改善整体患者疗法和 通过结合诊断和特定的治疗特性来结合结果。尽管纳米颗粒允许独特 在不同疾病的治疗领域的优势，诊断和治疗的结合 单个纳米颗粒中的方式可能与某些困难有关。因此，可能是理想的选择 开发一个单独但集成的多粒子系统，用于治疗药物。癌症检测的效率 通过磁共振成像（MRI）和原发性肿瘤和转移的化学疗法可以是 通过针对含有造影剂或抗癌药物的纳米颗粒的靶向显着改善 到癌细胞。因此，计划调查的总体目标包括开发， MRI的多粒子癌为诊断系统的多粒子癌靶向系统的体内表征和临床前测试 以及原发性肿瘤和转移的化学疗法。在目前的治疗研究中，氧化锰 纳米颗粒（MN3O4）将用作MRI对比剂。水溶性抗癌药物紫杉醇不良 （PTX） - 作为抗癌药物；中性脂质体 - 作为PTX的载体；改良的黄体激素 释放马龙（LHRH）胡椒 - 作为靶向部分。开发的多粒子疗法系统将 使用人类卵巢和肺癌的鼠模型在体外和体内进行测试。但是，提议 其他类型的载体/颗粒，对比剂和抗癌药物也可以扩展方法 作为其他类型的癌症。该提案的具体目的是：（1）合成和表征癌症 - 靶向纳米颗粒，用于成像和治疗癌症； （2）评估合成的效率 纳米颗粒作为MRI对比剂，用于使用鼠在体内检测原发性肿瘤和转移剂 肺癌和卵巢癌的模型； （3）评估配方奶和药物输送路线对整个的影响 紫杉醇的身体组织处置和药代动力学和（4）检查体内抗肿瘤效率和 与靶向癌症的脂质体的联合成像和化学疗法的不良副作用 静脉注入和吸入后，使用肺癌的原位鼠模型含有PTX。这是 期望提出的方法以及开发的癌症基于纳米颗粒的MRI的使用 对比剂和化学治疗药物将大大提高原发性检测的效率 癌症的肿瘤和转移和癌症的治疗，同时限制了治疗的不良副作用。这 计划的研究有可能显着影响成像和药物输送的领域并改善 肺和其他类型的癌症治疗的效率。

项目成果

Targeted Nanotherapeutics for Respiratory Diseases: Cancer, Fibrosis, and Coronavirus.

• DOI: 10.1002/adtp.202000203
• 发表时间: 2021-03
• 期刊: Advanced therapeutics
• 影响因子: 4.6
• 作者: Majumder J;Minko T
• 通讯作者: Minko T

Prevention of paclitaxel-induced neuropathy by formulation approach.

• DOI: 10.1016/j.jconrel.2019.04.013
• 发表时间: 2019-06
• 期刊: Journal of controlled release : official journal of the Controlled Release Society
• 作者: Xiaowei Zang;Jong Bong Lee;K. Deshpande;O. Garbuzenko;T. Minko;L. Kagan

Nanotherapeutics for Nose-to-Brain Drug Delivery: An Approach to Bypass the Blood Brain Barrier.

• DOI: 10.3390/pharmaceutics13122049
• 发表时间: 2021-11-30
• 期刊: Pharmaceutics
• 影响因子: 5.4
• 作者: Lee D;Minko T
• 通讯作者: Minko T

Development of Liposomal Vesicles for Osimertinib Delivery to EGFR Mutation-Positive Lung Cancer Cells.

• DOI: 10.3390/pharmaceutics12100939
• 发表时间: 2020-09-30
• 期刊: Pharmaceutics
• 影响因子: 5.4
• 作者: Skupin-Mrugalska P;Minko T
• 通讯作者: Minko T

Pharmacokinetics of inhaled nanotherapeutics for pulmonary delivery.

• DOI: 10.1016/j.jconrel.2020.07.011
• 发表时间: 2020-10-10
• 期刊: Journal of controlled release : official journal of the Controlled Release Society
• 作者: Shen AM;Minko T
• 通讯作者: Minko T