Emory-GA Tech Nanotechnology Center for Personalized an*

这项申请提出了一个跨学科的癌症纳米技术卓越中心（CCNE），该中心将把纳米技术与癌症生物分子特征（生物标志物）结合起来，用于个性化和预测肿瘤学。首要的科学重点是加速发展用于癌症分子成像、分子谱分析和个性化治疗的生物共轭纳米颗粒。本研究将进一步开发新的纳米颗粒试剂，共同靶向骨转移过程中涉及的信号转导通路及其微环境。本研究广泛适用于肺癌、结直肠癌、卵巢癌、脑肿瘤、淋巴瘤等多种类型的恶性肿瘤；但是概念验证研究的重点是人类前列腺癌和乳腺癌及其临床侵袭性表型——包括对癌细胞的询问和患者组织活检。一个令人信服的原因是，乳腺癌和前列腺癌在人类肿瘤学中代表了许多令人信服的挑战和机遇，如高发病率和死亡率，有证据表明靶向治疗可以提高这些癌症的生存率，以及我们与NCI前列腺癌和乳腺癌研究卓越专业项目（SPORE）的联系。CCNE有6个“协同项目”，每个团队都有纳米技术、生物工程、临床肿瘤学和基础癌症生物学方面的专业知识。项目1将开发用于癌症分子成像（Nie）的量子点和靶向纳米颗粒。项目2将开发用于单个癌细胞基因表达研究的新型分子信标和可激活纳米探针（Bao）。项目#3将优化和翻译“纳米分型”抗体连接量子点的多色集到多种癌症生物标志物，可以预测临床结果和对肿瘤医学信号转导抑制剂的敏感性（Simons/O'Regan）。项目#4将开发表面增强拉曼光谱（SERS）纳米标签和原子纳米团簇，用于癌症病理的分子分析（Natan/Young）。项目5将使用一种新的自组装和可生物降解纳米颗粒（Shin）开发纳米颗粒抗癌疗法。项目#6将专注于基本的癌症转移生物学和通过生物偶联纳米颗粒创造新的试剂来靶向转移癌细胞克隆及其骨基质微环境（Chung）。这些项目由5个核心功能支持：纳米材料的合成和制造（核心1 -王志强）；生物计算和生物信息学（核心2 - M. Wang）；组织标本和动物肿瘤模型（Core 3 - Datta）；onconnotechnology教育和推广（核心4 - Simons）；中心管理、生物统计支持、技术评估和商业化（核心5 - Nie/Simons/Murdock）。该CCNE通过与三个NCI CCCs的合作、乔治亚研究联盟、乔治亚癌症联盟和工业合作伙伴的投资而得到加强。CCNE嵌入Winship癌症研究所，这是一个新的28万平方英尺的综合癌症研究和护理大楼，并有一个特殊的美国合作伙伴，美国癌症协会和疾病控制中心，加速纳米技术的发现和临床转化，以减轻人类癌症的负担。

This application proposes a cross-disciplinary Center of Cancer Nanotechnology Excellence (CCNE) at Emory University and Georgia Tech that will integrate nanotechnology with cancer biomolecular signatures (biomarkers) for personalized and predictive oncology. The overarching scientific focus is to accelerate the development of bioconjugated nanoparticles for cancer molecular imaging, molecular profiling, and personalized therapy. The proposed research will further develop new nanoparticle reagents for co-targeting signal transduction pathways and its microenvironments that are involved in bone metastasis. This research is broadly applicable to many types of malignant tumors such as lung cancer, colorectal carcinoma, ovarian cancer, brain tumors, and lymphomas; but proof of concept research is focused on human prostate and breast cancers and their clinically aggressive phenotypes - including interrogations of cancer cells and patient tissue biopsies. A compelling reason for this focus is that breast and prostate cancers represent a number of compelling challenges and opportunities in human oncology such as high incidence and mortality, evidence that targeted therapies can improve survival in these cancers, and our linkages to NCI Specialized Programs of Research Excellence (SPORE) in both prostate and breast cancers. The CCNE has 6 "synergistic projects" with crossdisciplinary teams, each with expertise in nanotechnology, bioengineering, clinical oncology, and basic cancer biology. Project #1 will develop quantum dots and targeted nanoparticles for cancer molecular imaging (Nie). Project #2 will develop novel molecular beacons and activatable nanoprobes for gene expression studies of single cancer cells (Bao). Project #3 will optimize and translate "nanotyping" multicolor sets of antibody linked quantum dots to multiplex cancer biomarkers that can predict clinical outcomes and susceptibility to signal transduction inhibitors in medical oncology (Simons/O'Regan). Project #4 will develop surface-enhanced Raman spectroscopic (SERS) nanotags and atomic nanoclusters for molecular profiling in cancer pathology (Natan/Young). Project #5 will develop nanoparticle anti-cancer therapeutics using a new class of self-assembled and biodegradable nanoparticles (Shin). Project #6 will focus on basic cancer metastasis biology and creation of new reagents via bioconjugated nanoparticles to target metastatic cancer cell clones and their bone stromal microenvironments (Chung). These projects are supported by 5 core functions: nanomaterials synthesis and fabrication (Core 1 - Z. Wang); biocomputing and bioinformatics (Core 2 - M. Wang); tissue specimens and animal tumor models (Core 3 - Datta); onconanotechnology education and outreach (Core 4 - Simons); and center administration, biostatistics support, technology assessment, and commercialization (Core 5 - Nie/Simons/Murdock). This CCNE is strengthened by collaborations with three NCI CCCs, investment from the Georgia Research Alliance, Georgia Cancer Coalition, and industrial partners. The CCNE is embedded in the Winship Cancer Institute, a new integrated 280K sq ft cancer research and care building, and has a special constellation of US partners, the American Cancer Society and the Centers for Disease Control, for accelerating the discovery and clinical translation of nanotechnology to reducing the burden of human cancer.