Nanosensor-Based Phenotypic Screening for Precision Therapy of Cancer Stem Cells

基于纳米传感器的表型筛选用于癌症干细胞的精准治疗

• 批准号: 9371612
• 负责人: Arthur M Mercurio
• 金额: $ 30万
• 依托单位: UNIVERSITY OF MASSACHUSETTS AMHERST
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-12 至 2019-09-10
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9371612
• 关键词: Animals; Behavior; Biological Markers; Breast Cancer Cell; Breast Cancer Patient; Breast Carcinoma; Cancer Biology; Cell model; Cell surface; Cells; Characteristics; Data; Development; Drug usage; Fingerprint; Fluorescence; Goals; Gold; In Vitro; Individual; Mammary Neoplasms; Measurement; Measures; Methods; Neoplasm Metastasis; Output; Patients; Phenotype; Polymers; Population; Precision therapeutics; Preclinical Drug Evaluation; Process; Property; Proteins; Recurrence; Research; Research Personnel; Resistance; Screening for cancer; Solid Neoplasm; Stem cells; System; Techniques; Testing; Therapeutic; Therapeutic Agents; Therapeutic Uses; Toxic effect; Training; Xenograft procedure; analog; base; cancer stem cell; chemotherapy; cytotoxicity; drug discovery; drug mechanism; effective therapy; high throughput screening; in vivo; individual patient; malignant breast neoplasm; molecular phenotype; nanomaterials; nanoparticle; nanosensors; neoplastic cell; new therapeutic target; novel therapeutics; particle; personalized medicine; personalized therapeutic; programs; screening; self-renewal; sensor; small molecule; stemness; therapeutic target; tool; tumor; tumor xenograft

Project Summary/Abstract Nanosensor-Based Phenotypic Screening for Precision Therapy of Cancer Stem Cells Cancer stem cells (CSCs) have stem cells characteristics, including the ability to self-renew and populate new tumors. These cells are resistant to chemotherapy and are responsible for tumor recurrence and metastasis, making them important yet challenging therapeutic targets. In this U01 proposal, we will use a nanoparticle-based sensor to rapidly phenotype CSCs, using this information to screen for small molecule and nanoparticle therapeutics capable of differentiating CSCs to cells that are less aggressive and more susceptible to chemotherapeutics. Aim 1: Rotello will develop a robust nanoparticle-polymer high throughput-high content screening (HT-HCS) process for discriminating between CSC and non-CSC tumor cell models developed by Mercurio. Aim 2: Rotello will use the HT-HCS platform to identify small molecule and nanoparticle therapeutic agents with selective in vitro toxicity to CSC cells, and Mercurio will validate their ability to impact the in vitro and in vivo behavior of breast cancer cells. Aim 3: Mercurio will isolate CSCs from patient-dervied xenografts (PDX), and Rotello will use the HT-HCS platform to indentify precision therapeutic strategies in vitro that will be tested by Mercurio for their ability to hinder the initiation and recurrence of individual tumors. This ambitious research integrates the cancer biology expertise of Mercurio (UMass Worcester) with the nanomaterials and sensing capabilities of Rotello (UMass Amherst). The research will be greatly facilitated by the complementary team of researchers assembled for the project, as well as the extensive animal capabilities at Worcester and state of the art nanomaterials facilities at Amherst.

项目概要/摘要 基于纳米传感器的表型筛选用于癌症干细胞的精准治疗 癌症干细胞（CSC）具有干细胞特征，包括自我更新和自我更新的能力 填充新的肿瘤。这些细胞对化疗有抵抗力并导致肿瘤 复发和转移，使其成为重要但具有挑战性的治疗靶点。在这个 U01 提案，我们将使用基于纳米颗粒的传感器来快速对 CSC 进行表型分析，使用该传感器 用于筛选能够区分的小分子和纳米颗粒疗法的信息 CSCs 是侵袭性较小且对化疗更敏感的细胞。 目标 1：Rotello 将开发一种坚固的纳米颗粒聚合物高通量高含量 用于区分 CSC 和非 CSC 肿瘤细胞模型的筛选 (HT-HCS) 过程 由 Mercurio 开发。 目标2：Rotello将使用HT-HCS平台识别小分子和纳米颗粒 对 CSC 细胞具有选择性体外毒性的治疗剂，Mercurio 将验证其 影响乳腺癌细胞的体外和体内行为的能力。 目标 3：Mercurio 将从患者来源的异种移植物 (PDX) 中分离 CSC，而 Rotello 将使用 HT-HCS 平台可确定体外精准治疗策略，并由 Mercurio 因其能够阻止个体肿瘤的发生和复发而闻名。 这项雄心勃勃的研究整合了 Mercurio（麻省大学伍斯特分校）的癌症生物学专业知识 具有 Rotello（麻省大学阿默斯特分校）的纳米材料和传感能力。该研究将 为该项目组建的互补研究团队将极大地促进这一工作，因为 以及伍斯特广泛的动物能力和最先进的纳米材料 阿默斯特的设施。