Prostate Cancer Therapy with Annexin II Nanoparticles

膜联蛋白 II 纳米颗粒治疗前列腺癌

• 批准号: 7051975
• 负责人: JAMBOOR K. VISHWANATHA
• 金额: $ 11.93万
• 依托单位: UNIVERSITY OF NORTH TEXAS HLTH SCI CTR
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-08 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7051975
• 关键词: angiogenesis; annexins; apoptosis; athymic mouse; biotechnology; cell line; cell migration; cell proliferation; disease /disorder model; flow cytometry; gene expression; gene therapy; mixed tissue /cell culture; molecular oncology; nanotechnology; neoplasm /cancer blood supply; neoplasm /cancer genetics; neoplastic cell; neoplastic growth; particle; phenotype; proliferating cell nuclear antigen; prostate neoplasms

DESCRIPTION (provided by applicant): Annexin II expression is lost during progression of prostate cancer from the prostate intraepithelial neoplasia (PIN) stage to cancer. Annexin II functions both at the cell surface and in the nucleus: At the cell surface, Annexin II organizes a proteolytic center proposed to regulate angiogenesis, tumor invasion and metastasis. Annexin II in the cell nucleus regulates cell proliferation and DNA synthesis. The long-term goal of our research program is to identify the key molecular events that lead to development and progression of prostate cancer, in order that improved detection methods and therapies to treat this disease can be developed. The objective of studies outlined in this application is to determine if replacement of the Annexin II gene results in inhibition of prostate cancer growth and angiogenesis. Our central hypothesis is that the nanoparticle-mediated sustained expression of Annexin II gene would lead to prolonged accumulation of Annexin II in the nucleus resulting in inhibition of cell proliferation and sustained cell surface Annexin II expression resulting anti-angiogenesis, collectively inhibiting prostate cancer growth. We propose the following specific aims: Aim 1: To determine the in vitro effect of nanoparticle-mediated Annexin II delivery on phenotypes associated with prostate cancer growth. The working hypothesis for this aim, based upon preliminary data, is that sustained nanoparticle- mediated nuclear accumulation of Annexin II results in inhibition of prostate cancer cell proliferation. Aim 2: To determine the effect of nanoparticle-mediated Annexin II delivery on growth and angiogenesis of prostate tumors in a mouse model system. The working hypothesis for this aim is that sustained delivery of the anti-angiogenic Annexin II to prostate tumors in mice leads to reduction in tumor number and volume, and prolongs animal survival. These studies are innovative in that we are proposing a new approach of Annexin ll-based therapy for prostate cancer. At the completion of this project, it is our expectation that we will have determined that the nanoparticle-mediated sustained Annexin II gene delivery would result in retardation of prostate growth and reduced tumor burden.

描述（由申请人提供）：Annexin II 表达在 前列腺癌从前列腺上皮内瘤变 (PIN) 阶段发展为癌症。膜联蛋白 II 在细胞表面和细胞核中均发挥作用：在细胞表面，膜联蛋白 II 组织蛋白水解中心，旨在调节血管生成、肿瘤侵袭和转移。细胞核中的膜联蛋白 II 调节细胞增殖和 DNA 合成。我们研究计划的长期目标是确定导致前列腺癌发生和进展的关键分子事件，以便开发改进的检测方法和疗法来治疗这种疾病。本申请中概述的研究目的是确定膜联蛋白 II 基因的替换是否会导致前列腺癌生长和血管生成的抑制。我们的中心假设是，纳米颗粒介导的膜联蛋白 II 基因的持续表达将导致膜联蛋白 II 在细胞核中的长期积累，从而抑制细胞增殖，而细胞表面膜联蛋白 II 的持续表达导致抗血管生成，从而共同抑制前列腺癌的生长。我们提出以下具体目标： 目标 1：确定纳米颗粒介导的膜联蛋白 II 递送对前列腺癌生长相关表型的体外影响。基于初步数据，该目标的工作假设是，纳米颗粒介导的膜联蛋白 II 持续核积累会抑制前列腺癌细胞增殖。 目标 2：确定纳米颗粒介导的膜联蛋白 II 递送对小鼠模型系统中前列腺肿瘤生长和血管生成的影响。该目标的工作假设是，将抗血管生成膜联蛋白 II 持续递送至小鼠前列腺肿瘤可导致肿瘤数量和体积减少，并延长动物存活时间。 这些研究的创新之处在于我们提出了一种基于膜联蛋白 II 的前列腺癌治疗新方法。在该项目完成时，我们期望我们将确定纳米颗粒介导的持续膜联蛋白 II 基因递送将导致前列腺生长延迟并减少肿瘤负荷。

项目成果

Efficient nanoparticle mediated sustained RNA interference in human primary endothelial cells.

• DOI: 10.1088/0957-4484/22/44/445101
• 发表时间: 2011-11-04
• 期刊: Nanotechnology
• 影响因子: 3.5
• 作者: Mukerjee A;Shankardas J;Ranjan AP;Vishwanatha JK
• 通讯作者: Vishwanatha JK

Formulation, characterization and evaluation of curcumin-loaded PLGA nanospheres for cancer therapy.

• 发表时间: 2009-10
• 期刊: Anticancer research
• 影响因子: 2
• 作者: A. Mukerjee;J. Vishwanatha

Bioinspired Nanoparticles Engineered for Enhanced Delivery to the Bone.

• DOI: 10.1021/acsanm.9b01226
• 发表时间: 2019-10-25
• 期刊: ACS applied nano materials
• 影响因子: 5.9
• 作者: Gdowski AS;Lampe JB;Lin VJT;Joshi R;Wang YC;Mukerjee A;Vishwanatha JK;Ranjan AP
• 通讯作者: Ranjan AP