Engineering of Nano-based therapeutics for Optimized Outcome in Cancer Therapy

纳米技术领域目前在许多方面正在经历爆炸性的发展。这项技术有望产生创新，并在基于纳米的癌症治疗中发挥关键作用。在其他纳米粒子系统中，金纳米粒子(GNPs)在癌症治疗中的应用取得了巨大的进展，因为它们可以作为放射治疗的辐射剂量增强剂，也可以作为化疗的抗癌药物载体。然而，我们仍然不知道如何将这两种广泛使用的癌症治疗技术结合起来，利用GNPs的这些特性对癌细胞造成最大的损害。因此，这项拟议的研究计划的目标是设计GNP介导的放射治疗和化疗(将被称为化学放射治疗)的组合，以在癌症治疗中产生更好的结果。在过去的四年里，我的研究小组通过发表15篇文章，开发了优化GNP介导的放射治疗和GNP介导的药物输送的方案。我们相信，GNP介导的化疗放射将使我们能够设计一种非常积极的治疗方法来杀死癌细胞。此外，大多数基于GNP的辐射研究一直集中在光子的使用上。然而，最近的研究表明，如果我们可以用质子代替光子进行辐射治疗，结果是有希望的。这项拟议研究计划的第二个目标是建立一个基于NP的平台，利用体外细胞模型来阐明光子和质子之间的治疗结果差异。这项研究的结果将开启一场关于在加拿大使用质子疗法与光子疗法的全新讨论，因为质子疗法在加拿大几乎没有使用，而世界其他地区正在使用质子疗法。*这项研究为加拿大提供了三大战略好处。首先，预期的结果为旨在优化基于NP的癌症治疗的长期研究奠定了基础。癌症治疗药物的改进将降低医疗成本，同时提高癌症患者的生活质量。其次，这项研究的结果将通过培训三名博士生和两名硕士学生来支持加拿大在自然科学方面的领导地位，他们将获得解决问题的技能、独立性和癌症研究方面的专业知识。这些技能和知识对于帮助加拿大保持和改善其作为北美最大的纳米生物技术集群之一的地位至关重要。第三，我的实验室有能力成为使用GNPs进行癌症治疗的领先者。我被邀请参加AAPM和ASTRO(两个主要会议)的三人专家小组。我是MD安德森癌症中心、哈佛医学院和东北大学之间主要合作网络的一部分。这项前沿工作将提高加拿大在全球的学术形象，并为高技能劳动力提供人才。**

The field of nanotechnology is currently undergoing explosive development on many fronts. The technology is expected to generate innovations and play a critical role in nano-based cancer therapeutics. Among other nanoparticle (NP) systems, there has been tremendous progress made in the use of gold NPs (GNPs) in cancer therapy since they can be used as a radiation dose enhancer in radiation therapy and as well as an anticancer drug carrier in chemotherapy. However, we still do not know how to combine these two widely used cancer therapeutic therapy techniques using these properties of GNPs to cause the maximum damage to cancer cells. Hence, the goal of this proposed research program is to engineer a combination of GNP-mediated radiation therapy and chemotherapy (will be refereed to as chemoradiation) to yield a better outcome in cancer therapy. My research group has developed protocols to optimize GNP-mediated radiation therapy and GNP-mediated drug delivery through publication of 15 articles in the last four years. We believe that GNP-mediated chemoradiation would allow us to design a very aggressive treatment approach to kill cancer cells.****In addition, most of the GNP-based radiation research has been focused on the use of photons. However, recent studies have shown promising results if we can use protons for radiation treatment instead of photons. The second goal of this proposed research program is to build a NP-based platform to elucidate the therapeutic outcome differences between photons vs protons using in vitro cell models. The outcome of this research would open up a whole new discussion on the use of proton therapy vs photon therapy in Canada, since proton therapy is barely used in Canada while it is being used in other parts of the world.****This research offers three major strategic benefits to Canada. Firstly, the expected results are foundational for long-term research aiming at optimizing NP-based cancer therapeutics. The improved delivery of cancer therapeutics will reduce health care costs while improving the quality of life of cancer patients. Secondly, the results of this study will support Canada's leadership in natural sciences via the training of three PhD students and two MSc students, who will acquire problem-solving skills, independence, and expertise in cancer research. Such skills and knowledge are vital to helping Canada maintain and improve its position as one of largest nanobiotechnology clusters in North America. Thirdly, my lab is in a position to become a leader in the use of GNPs for cancer therapy. I was invited to be on the three-member expert panel at both AAPM and ASTRO (two major conferences). I am part of a major collaborative network between MD Anderson Cancer Centre, Harvard Medical School, and North Eastern University. This leading-edge work will enhance Canada's academic profile globally and provides personnel to a highly-skilled labor force.**