High Throughput Nanoimprint Manufacturing of Shape-Specific, Stimuli-Responsive Polymeric Nanocarriers for Drug and Imaging Agent Delivery

该奖项是根据2009年美国复苏和再投资法案（公法111-5）资助的。本研究的目的是开发纳米制造方法来制造形状特定的智能？能够根据疾病特异性或生理信号向目标组织输送药物或显像剂的纳米颗粒。具体来说，本研究开发了高通量、生物相容性的纳米印记制造工艺，以制造高度单分散、酶触发的药物和显像剂纳米载体。在自上而下的纳米压印过程中，纳米颗粒的大小和形状受到控制。实验旨在评估纳米颗粒的负载、药物和显像剂的释放，并表征纳米载体的大小和形状对细胞培养和微流体环境中载体运输和细胞摄取的影响。这项研究可以改变用于药物和显像剂输送的纳米颗粒的制造，并解决有关纳米载体的最佳尺寸和形状的基本问题。所获得的纳米载体可以显著改善癌症或心血管疾病等复杂疾病的治疗护理。此外，这项研究的结果不仅为制造具有疾病反应特性的药物输送载体提供了新的方向，而且还将探索利用纳米制造技术产生三维复杂结构的基本局限性和实际能力。如果成功，这将最终导致下一代疾病特异性和高效的治疗方法，并为纳米压印光刻技术提供新的生物医学应用。该项目本质上是跨学科的，涉及制造、机械和生物医学工程的原理。这为学生提供了一个独特而有益的教育环境，包括来自工程专业中代表性不足的群体的学生。在这里发展的结果和概念直接使一些研究生和本科课程受益，并通过研究人员积极参与短期课程和研讨会，为工业和K-12教师，学生和家长传播到工业和公众。

This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).The objective of this research is to develop nanomanufacturing methods for fabrication of shape-specific ?smart? nanoparticles capable of delivering drugs or imaging agents to targeted tissues in response to disease-specific or physiological signals. Specifically, high throughput, bio-compatible nanoimprint manufacturing processes are developed in this research to fabricate highly monodisperse, enzymatically-triggered nanoscale carriers of drug and imaging agents. The sizes and shapes of the nanoparticles are controlled during the top-down nano-imprint process. Experiments are carried out to evaluate nanoparticle loading, the release of drug and imaging agents, and to characterize the effects of nano-carrier size and shape on carrier transport and cellular uptake in cell cultures and microfluidic environments.This research can transform the manufacturing of nanoparticles for drug and imaging agent delivery as well as address fundamental questions regarding the optimal size and shape of nano-carriers. The obtained nano-carriers can significantly improve therapeutic care of complex diseases such as cancer or cardiovascular diseases. Moreover, the results from this research would not only provide new directions in fabricating drug delivery vehicles with disease-responsive properties, but would also explore the fundamental limitations and practical capabilities of generating three-dimensional, complex structures with nanomanufacturing techniques. If successful, this would eventually lead to the next generation of disease-specific and highly effective therapeutics and also provide novel biomedical applications for nanoimprint lithography. The project is inherently interdisciplinary and involves principles from manufacturing, mechanical, and biomedical engineering. This provides a unique and rewarding educational environment for the students involved including students from underrepresented groups in engineering professions. The results and concepts developed here directly benefit several graduate and undergraduate courses and are disseminated into industry and public by the active participations of the investigators in short courses and seminars for industry and K-12 teachers, students, and parents.