Nano-cocktail overcomes multidrug-resistance for ovarian cancer therapy

纳米鸡尾酒克服了卵巢癌治疗的多重耐药性

• 批准号: 8958102
• 负责人: Peisheng Xu
• 金额: $ 36.63万
• 依托单位: UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-01 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8958102
• 关键词: 2-methoxyestradiol; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Arts; Binding; Biodistribution; Biomedical Engineering; Biomedical Research; Cancer Etiology; Cell Proliferation; Cells; Cessation of life; Chemistry; Chemotherapy-Oncologic Procedure; Clinical Trials; Death Rate; Development; Diagnosis; Disease; Doctor of Pharmacy; Doxorubicin; Drug Carriers; Drug Combinations; Drug Kinetics; Drug resistance; ERBB2 gene; Encapsulated; Ensure; Environment; Equipment; Exhibits; Gynecologic; Head and Neck Neoplasms; Kinetics; Laboratories; Ligands; Malignant Neoplasms; Malignant neoplasm of ovary; Minnesota; Minority; Modeling; Modification; Monitor; Multi-Drug Resistance; Mus; NanoGel; Nature; Neoplasm Metastasis; Normal Cell; Operative Surgical Procedures; Oxidation-Reduction; Paclitaxel; Patients; Pharmaceutical Preparations; Pharmacologic Substance; Pharmacy Students; Polymers; Program Reviews; Property; Recruitment Activity; Regimen; Relapse; Research; Research Training; Resistance; Science; Scientist; Serum; Solid Neoplasm; South Carolina; Staging; Students; Survival Rate; System; Therapeutic Effect; Thinking; Toxic effect; Training; Tumor Debulking; Tumor Tissue; United States; Universities; Woman; Xenograft Model; Xenograft procedure; antitumor effect; base; cancer cell; cancer stem cell; cancer therapy; chemotherapy; college; density; effective therapy; experience; female reproductive system; fight against; graduate student; improved; intraperitoneal; killings; mortality; mouse model; nano; nanoparticle; nanoparticulate; next generation; novel; ovarian neoplasm; programs; public health relevance; receptor; response; sigma-2 receptor; skills; subcutaneous; success; tool; treatment strategy; tumor; tumor growth; undergraduate student; underrepresented minority student

 DESCRIPTION (provided by applicant): Ovarian cancer is the fifth most common cause of cancer-related deaths in women and results in more deaths than any other cancer of the female reproductive system. The primary reasons for the high death rate of ovarian cancer are multidrug-resistance and the metastatic nature of cancer stem cells (CSCs). Since conventional anticancer drugs cannot kill drug resistant cells and eliminate CSCs, a novel effective treatment for ovarian cancer is urgently needed. The objective of this research is to develop a dual targeted nano-cocktail (DTNC) for safe and effective ovarian cancer therapy. We hypothesize that: (a) the low density combination of two targeting moieties can minimize the non-specific targeting effect while ensuring that the drug carrier will be exclusively localized in the tumor tissue and taken up by cancer cells through hetero-multivalent binding; (b) the drug combination of different anticancer mechanisms will exhibit synergistic effects and eradicate ovarian tumor. Our project has three specific aims. In Aim 1, we will explore drug combinations for optimal cancer cell proliferation inhibitory effect. Aim 2 will examine the dual-ligand targeting effect on the biodistribution of DTNC and investigate its pharmacokinetic properties. Aim 3 will evaluate the tumor growth inhibitory effect of DTNC in both subcutaneous xenograft and orthotopic intraperitoneal tumor mouse models and examine its systemic toxicity. Over the course of this 3-year project, undergraduate, graduate, and Doctor of Pharmacy students will participate in the project in various levels, from hands-on skills with state-of-arts equipment to creative thinking. Undergraduate students will be recruited from the highly selective Honors College and Biomedical Engineering program of the University of South Carolina, as well as Morris College, a Historically Black, coeducational college. Therefore, the development of DTNC will provide clinicians with a more effective tool in fighting against ovarian cancer as well as offer precious biomedical research training opportunities for students, especially underrepresented minority students.

 描述（由适用提供）：卵巢癌是妇女与癌症相关死亡的第五大最常见原因，而与女性生殖系统的任何其他癌症相比，死亡人数更多。卵巢癌高死亡率高死亡率的主要原因是多药抗性和癌症干细胞（CSC）的转移性。由于常规的抗癌药不能杀死耐药细胞并消除CSC，因此迫切需要一种新型的卵巢癌有效治疗方法。这项研究的目的是开发双重靶向纳米鸡尾酒（DTNC），以进行安全有效的卵巢癌疗法。我们假设：（a）两个靶向部分的低密度组合可以最大程度地减少非特异性靶向效应，同时确保药物载体将仅本地定位在肿瘤组织中，并通过异种型结合被癌细胞吸收； （b）不同抗癌机制的药物组合将检查对我们项目的双配体靶向效应。我们的项目具有三个特定的目标。在AIM 1中，我们将探索用于最佳癌细胞增殖抑制作用的药物组合。 AIM 2将检查对双 - 配体的靶向效应 DTNC的生物分布并研究其药代动力学特性。 AIM 3将评估DTNC肿瘤生长抑制作用在皮下异种移植物和原位腹膜内肿瘤小鼠模型中的肿瘤生长抑制作用，并检查其全身毒性。在这个为期三年的项目中，本科生，研究生和药房的学生将以各种级别的级别参加该项目，从具有最先进的设备的动手技能到创意思维。本科生将从南卡罗来纳大学的高度选择性荣誉学院和生物医学工程课程中招募，以及历史悠久的黑人男女同校学院的莫里斯学院。因此，DTNC的开发将为临床医生提供更有效的与卵巢癌作斗争的工具，并为学生（尤其是代表性不足的少数族裔学生）提供宝贵的生物医学研究培训机会。