Nanoplatform-based combinational therapy against breast cancer

基于纳米平台的乳腺癌联合疗法

• 批准号: 8545104
• 负责人: Jin Xie
• 金额: $ 22.7万
• 依托单位: UNIVERSITY OF GEORGIA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8545104
• 关键词: ABCB1 gene; Abraxane; Accounting; Address; Amines; Chemotherapy-Oncologic Procedure; Complex; Doxorubicin; Drug Delivery Systems; Drug Kinetics; Drug resistance; Extravasation; Genes; Human; Investigation; Lead; Ligand Binding; Malignant Neoplasms; Nanoconjugate; Paclitaxel; Pharmaceutical Preparations; Regimen; Serum Albumin; Site; Small Interfering RNA; Tariquidar; Therapeutic; Therapeutic Agents; Therapeutic Effect; Time; Treatment Efficacy; base; cancer stem cell; cancer therapy; cell killing; chemotherapeutic agent; improved; inhibitor/antagonist; iron oxide; killings; magnetic field; malignant breast neoplasm; meetings; nanoparticle; neoplastic cell; novel; novel strategies; salinomycin; success; tumor

Among the obstacles to successful breast cancer chemotherapy, three have been critical: problems of drug delivery, drug resistance, and cancer stem cells (CSCs). Until now, no effort has been made to address all three issues in a single approach. This proposal seeks to meet the challenge through a nanoplatform that we recently developed, which is comprised of a human serum albumin (HSA) coating, an amine-rich intermediate coating, and an iron oxide nanoparticle (lONP) core. It structurally resembles Abraxane, a commercial paclitaxel-HSA complex, but has smaller hydrodynamic size therefore better tumor accumulation rate and extravasation rate. Such favorable pharmacokinetics can be further improved by adding an external field at the tumor sites, making the nanoplatform a promising drug delivery vehicle. With superior ligand binding capability afforded by both the outer HSA and intermediate amine-rich layers, such nanoplatform can load a broad range of drug molecules. In this proposal, we plan to load such a nanoplatform with doxorubicin (or paclitaxel), salinomycin and tariquidar (or siRNA that targets the MDR-1 gene). Doxorubicin (or paclitaxel) is a chemotherapeutic agent that is commonly used in breast cancer therapy, directed toward killing the differentiated tumor cells that account for most of a tumor mass. Salinomycin is a recently identified therapeutic agent with selective CSC killing capability. Both tariquidar and siRNA can function as MDR-1 inhibitors and their modulating effects may lead to increased drug accumulation. It is hoped that, with complementary cancer killing mechanisms and favorable tumor targeting profile provided by the nanoplatform, this novel approach may lead to dramatically improved therapeutic effects. This will be the first investigation on tumor therapy to address problems of drug delivery, drug resistance, and CSCs in a single approach. Success of this study may be a milestone in breast cancer therapy for providing a powerful, all-inone, breast cancer therapeutic regimen.

在乳腺癌化疗成功的障碍中，有三个至关重要：药物问题 递送、耐药性和癌症干细胞 (CSC)。到目前为止，尚未采取任何措施来解决所有问题 单一方法解决三个问题。该提案旨在通过我们的纳米平台应对挑战 最近开发的，它由人血清白蛋白 (HSA) 涂层组成，这是一种富含胺的物质 中间涂层和氧化铁纳米粒子（lONP）核心。它的结构类似于 Abraxane， 商业紫杉醇-HSA复合物，但具有较小的流体动力学尺寸，因此更好的肿瘤积累 率和外渗率。通过添加外部药物可以进一步改善这种有利的药代动力学。 肿瘤部位的场，使纳米平台成为有前途的药物输送工具。具有优越的配体 外部 HSA 和中间富含胺的层提供的结合能力，这种纳米平台可以 负载多种药物分子。在这个提案中，我们计划在这样的纳米平台上装载阿霉素 （或紫杉醇）、盐霉素和tariquidar（或针对 MDR-1 基因的 siRNA）。阿霉素（或紫杉醇） 是一种常用于乳腺癌治疗的化疗药物，旨在杀死癌细胞 占肿瘤块大部分的分化肿瘤细胞。盐霉素是最近发现的一种 具有选择性杀伤CSC能力的治疗剂。 tariquidar 和 siRNA 均可发挥 MDR-1 的作用 抑制剂及其调节作用可能导致药物蓄积增加。希望与 互补的癌症杀伤机制和有利的肿瘤靶向特性提供 纳米平台，这种新颖的方法可能会显着改善治疗效果。这将是第一个 研究肿瘤治疗以解决单一药物递送、耐药性和 CSC 问题 方法。这项研究的成功可能是乳腺癌治疗的一个里程碑，因为它提供了一种强大的、一体化的、 乳腺癌治疗方案。

项目成果

Ferritin nanocages: great potential as clinically translatable drug delivery vehicles?

铁蛋白纳米笼：作为临床可转化药物输送载体的巨大潜力？

• 发表时间: 2013-10
• 作者: Todd, Trever J;Zhen, Zipeng;Xie, Jin
• 通讯作者: Xie, Jin

Photostimulated near-infrared persistent luminescence as a new optical read-out from Crýýýýý-doped LiGaýýýOýýý.

光刺激近红外持续发光作为一种新的光学读出方式，来自掺杂 Cr 的 LiGa α O α α 。

• 发表时间: 2013
• 影响因子: 4.6
• 作者: Liu, Feng;Yan, Wuzhao;Chuang, Yen;Zhen, Zipeng;Xie, Jin;Pan, Zhengwei
• 通讯作者: Pan, Zhengwei

Casein-Coated Fe5C2 Nanoparticles with Superior r2 Relaxivity for Liver-Specific Magnetic Resonance Imaging.

酪蛋白涂层的 Fe5C2 纳米颗粒具有卓越的 r2 弛豫率，适用于肝脏特异性磁共振成像。

• 发表时间: 2015
• 影响因子: 12.4
• 作者: Cowger, Taku A;Tang, Wei;Zhen, Zipeng;Hu, Kai;Rink, David E;Todd, Trever J;Wang, Geoffrey D;Zhang, Weizhong;Chen, Hongmin;Xie, Jin
• 通讯作者: Xie, Jin

Improving detection specificity of iron oxide nanoparticles (IONPs) using the SWIFT sequence with long T(2) suppression.

使用长 T(2) 抑制的 SWIFT 序列提高氧化铁纳米颗粒 (IONP) 的检测特异性。

• 发表时间: 2014-07
• 影响因子: 2.5
• 作者: Wang, Luning;Tang, Wei;Zhen, Zipeng;Chen, Hongming;Xie, Jin;Zhao, Qun
• 通讯作者: Zhao, Qun

Fe5C2 nanoparticles with high MRI contrast enhancement for tumor imaging.

Fe5C2 纳米粒子具有高 MRI 对比度增强功能，用于肿瘤成像。

• 发表时间: 2014-04-09
• 作者: Tang, Wei;Zhen, Zipeng;Yang, Ce;Wang, Luning;Cowger, Taku;Chen, Hongmin;Todd, Trever;Hekmatyar, Khan;Zhao, Qun;Hou, Yanglong;Xie, Jin
• 通讯作者: Xie, Jin