CAREER: Engineering Plasmonic Nanoantenna Architectures for Efficient Nuclear Delivery & Advancing Awareness in Nanotechnology

这项职业计划旨在开发用于基因传递的可配置纳米结构。基因治疗最终依赖于纠正的基因有效地穿过细胞膜，最终到达细胞核，而不会暴露邻近的细胞。这项计划配置了纳米结构，以有效地、特别地将基因传递到细胞核。特别是，显示出独特光学性质的不对称构型将被开发成光学穿透膜，光学地通过拥挤的细胞内空间运输基因，并将基因直接运送到细胞核。有效和特定地传递正确的基因应该降低所需的剂量，并将不必要的副作用降至最低。这一策略还提供了一种新的基因传递系统，这种系统可以在传递后被光学移除，消除了基因传递系统本身的潜在副作用。作为更广泛影响和外联活动的一部分，该计划旨在提高对纳米技术的认识，并增加对STEM的参与人数不足。根据这项拟议的研究，将在毕业阶段设计实验室课程模块，在本科生水平实施研究职业系列，并将设计纳米技术顶峰讲习班，以吸引K-12学生参与STEM。这些结合的活动形成了一个框架，集成了研究、教育和跨PI职业生涯的推广。这一职业计划旨在解决基因传递系统面临的挑战，以有效地将基因传递到细胞核。这项拟议的工作将开发等离子体纳米天线体系结构--由非对称配置的纳米颗粒组成--能够进行光学传输、膜穿透和核基因释放，以实现高效的核传递。这项研究的智能价值在于配置了等离子体纳米天线结构，显示出高度的不对称性和耦合的纵模，以光谱方式将梯度力与辐射压力解耦。梯度力与辐射压力的光谱解耦首次允许在合理的光照度下的光学力，最大限度地减少光热诱导的布朗运动，以及在一个波长进行光传输而在另一个波长进行基因释放的光激活的多功能能力。以下工作支持本研究目标的实现：(1)确定等离子体纳米天线结构光传输的工作条件。(2)评估与光学失稳相比，光学力穿透是否提高穿透效率。(3)研究基因释放的空间调控是否改变了基因的表达。作为更广泛的影响和外联活动的一部分，该计划旨在提高对K-12、本科生和研究生对纳米技术和等离子的认识，并增加未被充分代表的学生参加科技、经济、技术和经济研究和培训课程。以下任务支持实现教育目标：(1)领导顶石研讨会，使K-12学生接触纳米技术。(2)实施科研生涯系列研讨会，把培养大学生对科研的兴趣作为一条职业道路。(3)扩展等离子体激活学研究生课程，加入实验模块。这些活动结合在一起，形成了一个集研究、教育和职业发展于一体的框架。

This CAREER plan aims to develop configurable nanostructures for gene delivery. Gene therapyultimately relies on corrected genes to be efficiently delivered across cell membranes and ultimatelyto the cell nucleus without exposing neighboring cells. This plan configures nanostructures todeliver genes efficiently and specifically to the cell nucleus. In particular, asymmetricconfigurations, displaying unique optical properties, will be developed to optically penetratemembranes, optically transport genes through the crowded intracellular space, and deliver genesdirectly to the nucleus. Efficient and specific delivery of corrected genes should lower requireddosages and minimize unwanted side effects. This strategy also offers a new class of gene deliverysystems which can be optically removed post-delivery, eliminating potential side effects from thegene delivery system itself. As part of broader impacts and outreach activities, this plan aims toadvance awareness in nanotechnology, and to increase underrepresented participation in STEM.Drawing from this proposed research, laboratory course modules will be designed at the graduatelevel, research career series will be implemented at the undergraduate level, and nanotechnologycapstone workshops will be designed to engage K-12 students in STEM. These combined activitiesserve to form a framework integrating research, education and outreach over the PI's career.This CAREER plan aims to address the challenge facing gene delivery systems to deliver genesefficiently and specifically to the cell nucleus. The proposed work will develop plasmonicnanoantenna architectures - consisting of asymmetrically configured nanoparticles - capable ofoptical transport, membrane penetration and nuclear gene release for efficient nuclear delivery. Theintellectual merit of the proposed research lies in the configuration of plasmonic nanoantennaarchitectures, displaying high degrees of asymmetry and coupled longitudinal modes, to spectrallydecouple the gradient force from the radiation pressure. Spectral decoupling of the gradient forcefrom the radiation pressure allows, for the first time, optical forces at reasonable light irradiances,minimized photothermally induced Brownian motion, and multi-functional capabilities whereoptical transport is conducted at one wavelength and optical activation of gene release is conductedat another wavelength. The following tasks support the attainment of the research goal: (1) Identifyoperation conditions for optical transport of plasmonic nanoantenna architectures. (2) Assesswhether optical force penetration compared to optical destabilization improves penetrationefficiency. (3) Investigate whether spatial modulation of gene release modifies resulting geneexpression. As part of broader impacts and outreach activities, this plan aims to advance awarenessin nanotechnology and plasmonics at the K-12, undergraduate and graduate level, and to increaseunderrepresented participation in STEM. The following tasks support the attainment of theeducational goal: (1) Lead capstone workshops to expose K-12 students to nanotechnology. (2)Implement research career seminar series to educate undergraduate students interested in researchas a career path. (3) Expand plasmonics graduate course curriculum to include laboratory modules.These combined activities serve to form a framework integrating research, education and outreachover the PI's career.