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（由申请人提供）：卵巢癌是女性癌症相关死亡的第五大常见原因，其死亡人数比女性生殖系统的任何其他癌症都要多。卵巢癌死亡率高的主要原因是多种药物。由于传统的抗癌药物无法杀死耐药细胞并消除CSC，因此迫切需要一种新的有效治疗卵巢癌的方法。我们的研究目标是开发一种双靶向纳米混合物（DTNC），用于安全有效的卵巢癌治疗：（a）两个靶向部分的低密度组合可以最大限度地减少非特异性靶向效应，同时确保药物载体。将专门定位于肿瘤组织并通过异多价结合被癌细胞吸收；（b）不同抗癌机制的药物组合将表现出协同作用并根除卵巢肿瘤。我们将探索药物组合以获得最佳的癌细胞增殖抑制效果。目标2将检查双配体靶向作用。 目标 3 将评估 DTNC 在皮下异种移植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。 ，药学博士生将参与各个级别的项目，从具有最先进设备的实践技能到创造性思维的本科生将从严格挑选的荣誉中招募。因此，DTNC的发展将为对抗卵巢癌提供更有效的工具，并提供宝贵的生物医学资源。为学生，特别是代表性不足的少数族裔学生提供研究培训机会。