Emory-GA Tech Nanotechnology Center for Personalized an*

这项申请建议在埃默里大学和佐治亚理工学院建立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签名(生物标记物)相结合，以实现个性化和预测性肿瘤学。最重要的科学焦点是加快开发用于癌症分子成像、分子图谱和个性化治疗的生物结合纳米颗粒。这项拟议的研究将进一步开发新的纳米粒子试剂，用于共靶向参与骨转移的信号转导通路及其微环境。这项研究广泛适用于许多类型的恶性肿瘤，如肺癌、结直肠癌、卵巢癌、脑瘤和淋巴瘤；但概念验证研究侧重于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。关注乳腺癌和前列腺癌的一个令人信服的原因是，乳腺癌和前列腺癌代表着人类肿瘤学中许多引人注目的挑战和机遇，例如高发病率和死亡率，靶向治疗可以提高这些癌症的存活率的证据，以及我们与NCI前列腺癌和乳腺癌卓越研究专门项目(SPORT)的联系。CCNE有6个跨学科团队的“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将开发新的分子信标和可激活的纳米探针，用于单个癌细胞(BaO)的基因表达研究。项目3将优化和转化抗体连接的多色量子点的“纳米”组，以多重癌症生物标记物，可以预测临床结果和对内科肿瘤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簇，用于癌症病理学中的分子图谱(Natan/Young)。项目5将使用一种新型的自组装和可生物降解的纳米颗粒(Shin)来开发纳米抗癌疗法。项目6将专注于基本的癌症转移生物学和通过生物结合纳米颗粒创造新的试剂，以靶向转移性癌细胞克隆及其骨基质微环境(Chung)。这些项目得到了5个核心职能的支持：纳米材料合成和制造(核心1-Z.Wang)；生物计算和生物信息学(核心2-M)；组织标本和动物肿瘤模型(核心3-Datta)；鱼类技术教育和推广(核心4-Simons)；以及中心管理、生物统计支持、技术评估和商业化(核心5-Nie/Simons/Murdock)。通过与三个NCI CCC的合作、佐治亚州研究联盟、佐治亚州癌症联盟和工业合作伙伴的投资，CCNE得到了加强。CCNE嵌入了Winship癌症研究所，这是一座新的280K平方英尺的综合癌症研究和护理大楼，并有一个由美国癌症协会和疾病控制中心组成的特殊合作伙伴星座，以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.