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.

项目摘要/摘要 基于纳米传感器的肿瘤干细胞精确治疗表型筛选 肿瘤干细胞(CSCs)具有干细胞特性，包括自我更新和 植入新的肿瘤。这些细胞对化疗有抵抗力，并与肿瘤有关。 复发和转移，使它们成为重要但具有挑战性的治疗靶点。在这 U01建议，我们将使用基于纳米颗粒的传感器来快速表型CSCs，使用 筛选能够区分小分子和纳米颗粒疗法的信息 CSCs向侵袭性较弱且对化疗药物更敏感的细胞分化。 目标1：罗特洛将开发一种强大的纳米粒子-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)方法 由Mercurio开发。 目标2：Rotello将使用HT-HCS平台来识别小分子和纳米粒子 对CSC细胞具有选择性体外毒性的治疗剂，Mercurio将验证其 影响乳腺癌细胞体外和体内行为的能力。 目标3：Mercurio将从患者分离的异种移植物(PDX)中分离CSCs，Rotello将使用 HT-HCS平台在体外确定精确的治疗策略，将通过 Mercurio有能力阻止个别肿瘤的发生和复发。 这项雄心勃勃的研究整合了摩科瑞(UMassWorcester)的癌症生物学专业知识 拥有罗特罗公司(UMassAmherst)的纳米材料和传感能力。这项研究将 由为该项目聚集的互补研究人员团队提供极大的便利，如 以及伍斯特大学广泛的动物能力和最先进的纳米材料 阿默斯特的设施。